Osteoporosis medical therapy: Difference between revisions

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==Overview==
==Overview==
The mainstays of treatment in primary [[osteoporosis]] [[disease]] are based on in life style modifications. Most of the time in high risk patients and people with past history of [[Osteoporosis|osteoporotic]] [[fracture]], [[Medical therapy template|medical therapy]] is necessary. [[Bisphosphonates]] are the '''''first line''''' treatment for [[osteoporosis]] [[disease]]. [[Raloxifene]] is the '''''second line''''' [[treatment]] of [[osteoporosis]] in [[postmenopausal]] women, for both [[treatment]] and [[prevention]]. [[Denosumab]] is a human [[monoclonal antibody]] designed to inhibit [[RANKL]] ([[RANK]] ligand), a [[protein]] that acts as the primary [[Signal (biology)|signal]] for [[bone]] removal. It is used to treat [[Osteoporosis]] in elder men and [[postmenopausal]] women. [[Teriparatide]] and Abaloparatide are human [[recombinant]] [[parathyroid hormone]]<nowiki/>s used to treat [[postmenopausal]] woman with [[osteoporosis]] at high risk of [[fracture]] or to increase [[bone]] mass in men with [[osteoporosis]].
The mainstay of treatment in primary osteoporosis is based on life style modifications. Most of the time in high risk patients and people with past history of osteoporotic [[fracture]], [[Medical therapy template|medical therapy]] is necessary. [[Bisphosphonates]] are the '''''first line''''' treatment for osteoporosis. [[Raloxifene]] is the '''''second line''''' [[treatment]] of osteoporosis in [[postmenopausal]] women, for both treatment and [[prevention]]. [[Denosumab]] is a human [[monoclonal antibody]] designed to inhibit [[RANKL]] ([[RANK]] ligand), a [[protein]] that acts as the primary [[Signal (biology)|signal]] for [[bone]] removal. It is used to treat osteoporosis in older men and [[postmenopausal]] women. [[Teriparatide]] and Abaloparatide are human [[recombinant]] [[parathyroid hormone]]<nowiki/>s used to treat [[postmenopausal]] osteoporosis in women with high risk of [[fracture]] or to increase [[bone]] mass in men with osteoporosis.


==Medical therapy==
==Medical therapy==
'''Fracture prevention medical therapy algorithm'''<ref name="pmid26370055">{{cite journal |vauthors=Papaioannou A, Santesso N, Morin SN, Feldman S, Adachi JD, Crilly R, Giangregorio LM, Jaglal S, Josse RG, Kaasalainen S, Katz P, Moser A, Pickard L, Weiler H, Whiting S, Skidmore CJ, Cheung AM |title=Recommendations for preventing fracture in long-term care |journal=CMAJ |volume=187 |issue=15 |pages=1135–44, E450–61 |year=2015 |pmid=26370055 |pmc=4610837 |doi=10.1503/cmaj.141331 |url=}}</ref>
'''Fracture prevention medical therapy algorithm'''<ref name="pmid26370055">{{cite journal |vauthors=Papaioannou A, Santesso N, Morin SN, Feldman S, Adachi JD, Crilly R, Giangregorio LM, Jaglal S, Josse RG, Kaasalainen S, Katz P, Moser A, Pickard L, Weiler H, Whiting S, Skidmore CJ, Cheung AM |title=Recommendations for preventing fracture in long-term care |journal=CMAJ |volume=187 |issue=15 |pages=1135–44, E450–61 |year=2015 |pmid=26370055 |pmc=4610837 |doi=10.1503/cmaj.141331 |url=}}</ref>
{{Family tree/start}}
{{Family tree/start}}
{{Family tree |boxstyle=text-align: left; | | | A01 | | | | | | | | B01 |A01='''Strategies to prevent [[fracture]]s and falls''' <br> <br> '''Recommend:''' <br> • Dietary calcium 1200 mg/day <br> <br>Suggest:<br> • Vitamin D (≥ 800–2000 IU/day)<br>• Calcium supplement≤ 500 mg, if dietary calcium not met <br> • Hip protectors<br>• Multifactorial fall-prevention strategies:<br>1. Exercise (balance, strength and functional training)<br>2. Medication reviews (e.g., Beers criteria)<br>3. Assessment of environmental hazards<br> 4. Use of assistive devices<br>5. Management of urinary incontinence|B01='''Fracture risk assessment on admission'''<br>• Prior hip fracture?<br>• Prior vertebral fracture?<br>• More than one prior fracture (excluding hands, feet, ankles)? <br> • Recent use of glucocorticoid and one prior fracture (excluding hands, feet, ankles)?<br> • Assessed as high risk for fracture and receiving fracture treatment before admission?<br> • Vertebral fracture present? (if chest radiography ordered, screen for vertebral fractures)}}
{{Family tree |boxstyle=text-align: left; | | | | A01 | | | | | | B01 |A01='''Strategies to prevent [[fracture]]s and falls''' <br> <br> '''Recommend:''' <br> • Dietary [[calcium]] 1200 mg/day <br> <br>'''Suggest:'''<br> • [[Vitamin D]] (≥ 800–2000 IU/day)<br>• [[Calcium]] supplement≤ 500 mg, if dietary [[calcium]] not met <br> • [[Hip]] protectors<br>• Multifactorial fall-prevention strategies:<br> 1. [[Exercise]] (balance, strength and functional training)<br> 2. [[Medication]] reviews (e.g., Beers criteria)<br> 3. Assessment of environmental hazards<br> 4. Use of assistive devices<br>5. Management of [[urinary incontinence]]|B01='''[[Fracture]] risk assessment<br> on admission'''<br>• Prior [[hip fracture]]?<br>• Prior [[vertebral fracture]]?<br>• More than one prior [[fracture]] <br>(excluding [[hands]], [[feet]], [[ankles]])? <br> • Recent use of [[glucocorticoid]] and prior<br> [[fracture]] (excluding [[hands]], [[feet]], [[ankles]])?<br> • Assessed as high risk for [[fracture]] and <br>receiving [[fracture]] treatment before admission?<br> • [[Vertebral fracture]] present?<br> (if chest [[radiography]] ordered,<br> screen for [[vertebral fractures]])}}
{{Family tree | | | | |!| | | | | | | |!| |!| | }}
{{Family tree | | | | |!| | | | | | |!| |!| | }}
{{Family tree | | | | |`|-|-|B01|-|-|'| |!| |B01= If patient has a fracture, reassess}}
{{Family tree | | | | |`|-|B01|-|-|'| |!|B01= If patient has <br>a [[fracture]], reassess}}
{{Family tree | | | | | | | | | | | | | |A01| |A01=If “yes’ to any of the above,<br>patient is considered as '''high risk'''}}
{{Family tree | | | | | | | | | | | | | |A01| |A01=If "yes" to any of the above,<br>patient is considered as '''high risk'''}}
{{Family tree | | | | | | | | | | | | | | |!| }}
{{Family tree | | | | | | | | | | | | | | |!| }}
{{Family tree | | | | | | | | | | |,|-|-|A01| |A04=Pharmacologic therapy not appropriate|A03=No|A02=Is patient expected to live > 1 year?|A01='''Recommend:'''<br>Dietary calcium 1200 mg/day<br>Vitamin D supplements (800–2000 IU/day)<br>Calcium supplements ≤ 500 mg, if dietary calcium not met<br>Hip protectors for mobile residents<br> <br>'''Suggest:'''<br>Exercise program only as part of multifactorial fracture and fall prevention program}}
{{Family tree | | | | | | | | | | |,|-|-|A01| |A04=[[Pharmacologic]] therapy not appropriate|A03=No|A02=Is patient expected to live > 1 year?|A01='''Recommend:'''<br> Dietary [[calcium]] 1200 mg/day<br> [[Vitamin D]] supplements (800–2000 IU/day)<br> [[Calcium]] supplements ≤ 500 mg, if dietary [[calcium]] not met<br> [[Hip]] protectors for mobile residents<br> <br>'''Suggest:'''<br> [[Exercise]] program only as part of multifactorial [[fracture]] and fall prevention program}}
{{Family tree | |A04|-|A03|-|A02| | | | |A04=Pharmacologic therapy not appropriate|A03=No|A02=Is patient expected to live > 1 year?}}
{{Family tree | |A04|-|A03|-|A02| | | | |A04=[[Pharmacologic]] therapy not appropriate|A03=No|A02=Is patient expected to live > 1 year?}}
{{Family tree | | | | | | | | | | |!| | | | | | | | | | | }}
{{Family tree | | | | | | | | | | |!| | | | | | | | | | | }}
{{Family tree | | | | | | | | | |A01| | | | | | | | | |A01=Yes}}
{{Family tree | | | | | | | | | |A01| | | | | | | | | |A01=Yes}}
{{Family tree | | | | | | | | | | |!| | | | | | | | | |}}
{{Family tree | | | | | | | | | | |!| | | | | | | | | |}}
{{Family tree | | | | | | | | | |A01| | | | | | | | | |A01=Is CrCl > 30 mL/min?}}
{{Family tree | | | | | | | | | |A01| | | | | | | | | |A01=Is CrCl > 30 mL/min?}}
{{Family tree | | | | | | | |,|-|-|^|-|-|.| | }}
{{Family tree | | | | | |,|-|-|-|-|-|^|-|-|-|.| | }}
{{Family tree | | | | | | | C01 | | | | C02 | | |C01= No|C02= Yes}}
{{Family tree | | | | | C01 | | | | | | | | C02 | | |C01= No|C02= Yes}}
{{Family tree | | | | | | | |!| | | | | |!| | }}
{{Family tree | | | | | |!| | | | | | | | | |!| | }}
{{Family tree | | | | | | | |!| | C01 |-| C02 |-| C03 | | |C01=Yes|C02= Does patient have dysphagia?|C03=No}}
{{Family tree | | | | | |!| | | | C01 |-|-| C02 | | | | |C01=Yes|C02= Does patient have [[dysphagia]]?}}
{{Family tree | | | | | | | |!| | |!| | | | | | | |!| |}}
{{Family tree | | | | | |!| | | | |!| | | | |!| | | | | |}}
{{Family tree | | | | | | | C01 | | C02 | | | | |C04|C01= For patients with CrCl 15–30 mL/min <br>'''Recommend:'''<br>• Denosumab<br>(60 mg subcutaneously twice yearly)<br>'''Remarks:'''<br>• Monitor calcium levels, given higher risk of hypocalcemia <br>• Bisphosphonate therapies are not recommended <br>• Consider referral to specialist|C02='''Recommend:'''<br>• Denosumab<br>(60 mg subcutaneously twice yearly)<br>• Zoledronic acid<br>(5 mg IV once yearly)<br> '''Suggest:'''<br>• Teriparatide<br>(20 mcg subcutaneously daily)|C04='''Recommend:'''<br>• Alendronate (70 mg weekly)<br>• Risedronate (35 mg weekly or 150 mg monthly)<br>• Denosumab (60 mg subcutaneously twice yearly)<br>• Zoledronic acid (5 mg IV once yearly)<br> '''Suggest:'''<br>• Teriparatide (20 mcg subcutaneously daily)}}
{{Family tree | | | | | |!| | | | |!| | | | A01 | | | | | |A01=No}}
{{Family tree | | | | | |!| | | | |!| | | | |!| | | | | |}}
{{Family tree |boxstyle=text-align: left; | | | | C01 | | | | C02 | | | C04 | | |C01= '''''For patients with CrCl 15–30 mL/min''''' <br>'''Recommend:'''<br>• [[Denosumab]]<br>(60 mg subcutaneously twice yearly)<br>'''Remarks:'''<br>• Monitor [[calcium]] levels, given higher risk of [[hypocalcemia]] <br>• [[Bisphosphonate]] therapies are not recommended <br>• Consider referral to specialist|C02='''Recommend:'''<br>• [[Denosumab]]<br>(60 mg subcutaneously twice yearly)<br>• [[Zoledronic acid]]<br>(5 mg IV once yearly)<br> '''Suggest:'''<br>• [[Teriparatide]]<br>(20 mcg subcutaneously daily)|C04='''Recommend:'''<br>• [[Alendronate]] (70 mg weekly)<br>• [[Risedronate]] (35 mg weekly or 150 mg monthly)<br>• [[Denosumab]] (60 mg subcutaneously twice yearly)<br>• [[Zoledronic acid]] (5 mg IV once yearly)<br> '''Suggest:'''<br>• [[Teriparatide]] (20 mcg subcutaneously daily)}}


{{Family tree/end}}
{{Family tree/end}}
 
Most of the time in high risk patients and people with past history of [[Oteoporosis|osteoporotic]] [[fracture]], [[Medical therapy template|medical therapy]] is necessary.<ref name="pmid28780668">{{cite journal| author=Minisola S, Cipriani C, Occhiuto M, Pepe J| title=New anabolic therapies for osteoporosis. | journal=Intern Emerg Med | year= 2017 | volume=  | issue=  | pages=  | pmid=28780668 | doi=10.1007/s11739-017-1719-4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28780668  }}</ref>
* Most of the time in high risk patients and people with past history of [[Osteoporosis|osteoporotic]] [[fracture]], [[Medical therapy template|medical therapy]] is necessary.<ref name="pmid28780668">{{cite journal| author=Minisola S, Cipriani C, Occhiuto M, Pepe J| title=New anabolic therapies for osteoporosis. | journal=Intern Emerg Med | year= 2017 | volume=  | issue=  | pages=  | pmid=28780668 | doi=10.1007/s11739-017-1719-4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28780668  }}</ref>


=== Medical therapy purpose ===
=== Medical therapy purpose ===
* The primary most important goal for treatment of [[osteoporosis]] is to reduce longtime [[fracture]] risk in patients. Increasing [[Bone mineral density|bone mineral density (BMD)]] in response to the treatment is far less important than improvement of clinical aspects of [[osteoporosis]], i.e., [[Osteoporosis|osteoporotic]] [[Bone fracture|fracture]]. Therefore, most of the [[drugs]]' efficacy are measured by the extend they improve the [[fracture]] risk, in turn of increasing [[Bone mineral density|BMD]].<ref name="pmid11893367">{{cite journal |vauthors=Cummings SR, Karpf DB, Harris F, Genant HK, Ensrud K, LaCroix AZ, Black DM |title=Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs |journal=Am. J. Med. |volume=112 |issue=4 |pages=281–9 |year=2002 |pmid=11893367 |doi= |url=}}</ref>
* The primary most important goal for treatment of [[osteoporosis]] is to reduce longtime [[fracture]] risk in patients. Increasing [[Bone mineral density|bone mineral density (BMD)]] in response to the treatment is far less important than improvement of clinical aspects of [[osteoporosis]], i.e., [[Osteoporosis|osteoporotic]] [[Bone fracture|fracture]]. Therefore, most of the [[drugs]] efficacy is measured by the extent it can improve the [[fracture]] risk.<ref name="pmid11893367">{{cite journal |vauthors=Cummings SR, Karpf DB, Harris F, Genant HK, Ensrud K, LaCroix AZ, Black DM |title=Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs |journal=Am. J. Med. |volume=112 |issue=4 |pages=281–9 |year=2002 |pmid=11893367 |doi= |url=}}</ref>
* It has to explain for patients that treatment purpose is to reduce their [[fracture]] risk in the future. During the treatment, if a single [[fracture]] happened, it is not necessarily reflect of treatment failure; despite the major complicates [[fractures]] that may need to start alternative treatments or patient referral to [[specialist]].<ref name="pmid28761958">{{cite journal |vauthors=Ensrud KE, Crandall CJ |title=Osteoporosis |journal=Ann. Intern. Med. |volume=167 |issue=3 |pages=ITC17–ITC32 |year=2017 |pmid=28761958 |doi=10.7326/AITC201708010 |url=}}</ref>
* During the treatment, if a single [[fracture]] happens, it may not necessarily reflect treatment failure; and may need to start alternative treatments or patient referral to [[specialist]].<ref name="pmid28761958">{{cite journal |vauthors=Ensrud KE, Crandall CJ |title=Osteoporosis |journal=Ann. Intern. Med. |volume=167 |issue=3 |pages=ITC17–ITC32 |year=2017 |pmid=28761958 |doi=10.7326/AITC201708010 |url=}}</ref>
* [[Calcium]] and [[vitamin D]] supplementation have been found to be effective in reducing the long term [[Bone fracture|fracture]] risk, significantly. In order to suggest the people to use [[vitamin D]] and [[calcium]] [[supplements]], first the [[physician]] has to become sure that patient is not able to obtain the [[nutrients]] through daily intake. The available supplemental ions of [[calcium]] include [[calcium carbonate]] and [[calcium citrate]]; and [[vitamin D3]] has various [[Dosage form|dosage forms]].<ref name="pmid24131178">{{cite journal |vauthors=Bauer DC |title=Clinical practice. Calcium supplements and fracture prevention |journal=N. Engl. J. Med. |volume=369 |issue=16 |pages=1537–43 |year=2013 |pmid=24131178 |pmc=4038300 |doi=10.1056/NEJMcp1210380 |url=}}</ref>
* [[Calcium]] and [[vitamin D]] supplementation have been found to be effective in reducing the long term [[Bone fracture|fracture]] risk, significantly. In order to suggest the people to use [[vitamin D]] and [[calcium]] [[supplements]], first the [[physician]] has to become sure that patient is not able to obtain the [[nutrients]] through daily intake. The available supplemental ions of [[calcium]] include [[calcium carbonate]] and [[calcium citrate]]; and [[vitamin D3]].<ref name="pmid24131178">{{cite journal |vauthors=Bauer DC |title=Clinical practice. Calcium supplements and fracture prevention |journal=N. Engl. J. Med. |volume=369 |issue=16 |pages=1537–43 |year=2013 |pmid=24131178 |pmc=4038300 |doi=10.1056/NEJMcp1210380 |url=}}</ref>


=== Medical therapy candidates ===
=== Medical therapy candidates ===
* The national [[osteoporosis]] foundation (NOF) declare that [[osteoporosis]] treatment has to prescribed for followings:
* The National [[osteoporosis]] foundation (NOF) has declared following prescription for [[osteoporosis]] treatment:
** Elder men and [[postmenopausal]] women with past history of [[Osteoporosis|osteoporotic]] [[Bone fracture|fracture]]
** Elder men and [[postmenopausal]] women with past history of [[Osteoporosis|osteoporotic]] [[Bone fracture|fracture]]
** Elder man and [[postmenopausal]] women with [[Bone mineral density|BMD]]-identified [[osteoporosis]] (T-score ≤ -2.5 [[Standard deviation|SD]])
** Elder man and [[postmenopausal]] women with [[Bone mineral density|BMD]]-identified [[osteoporosis]] (T-score ≤ -2.5 [[Standard deviation|SD]])
** Elder man and [[postmenopausal]] women with -1.0 > T-score > -2.5 SD with high risk of [[Osteoporosis|osteoporotic]] [[Bone fracture|fracture]]
** Elder man and [[postmenopausal]] women with -1.0 > T-score > -2.5 SD with high risk of [[Osteoporosis|osteoporotic]] [[Bone fracture|fracture]]
** Men with [[hypogonadism]] that [[testosterone]] therapy is contraindicated<ref name="pmid28761958" />
** Men with [[hypogonadism]] in whom [[testosterone]] therapy is contraindicated<ref name="pmid28761958" />
* The international osteoporosis foundation (IOF) suggested that postmenopausal women and men age 50 and older presenting with the following should be considered for treatment:  
* The International [[osteoporosis]] foundation (IOF) suggested that [[postmenopausal]] women and men age 50 and older presenting with the following should be considered for treatment:  
** A hip or vertebral fracture (clinically apparent or found on vertebral imaging). There are abundant data that patients with spine and hip fractures will have reduced fracture risk if treated with pharmacologic therapy. This is true for fracture patients with BMD in both the low bone mass and osteoporosis range . In patients with a hip or spine fracture, the T-score is not as important as the fracture itself in predicting future risk of fracture and antifracture efficacy from treatment.
** A [[hip]] or [[vertebral fracture]] (clinically apparent or found on [[vertebral]] imaging). There are abundant data that patients with [[spine]] and [[hip fractures]] will have reduced fracture risk if treated with [[pharmacologic]] [[therapy]]. This is true for [[fracture]] patients with [[Bone mineral density|BMD]] in both the low [[bone mass]] and [[osteoporosis]] range . In patients with a [[Hip Fractures|hip]] or [[spine]] [[fracture]], the T-score is not as important as the [[fracture]] itself in predicting [[future]] risk of [[fracture]] and antifracture efficacy from treatment.
** T-score ≤−2.5 at the femoral neck, total hip, or lumbar spine. There is abundant evidence that the elevated risk of fracture in patients with osteoporosis by BMD is reduced with pharmacotherapy [52, 57, 59–70].
** T-score ≤−2.5 at the [[femoral neck]], total [[hip]], or [[lumbar spine]]. There is abundant evidence that the elevated risk of [[fracture]] in patients with [[osteoporosis]] by [[Bone mineral density|BMD]] is reduced with [[pharmacotherapy]].
** Low bone mass (T-score between −1.0 and −2.5 at the femoral neck or lumbar spine) and a 10-year probability of a hip fracture ≥3 % or a 10-year probability of a major osteoporosis-related fracture ≥20 % based on the US adapted WHO algorithm.<ref name="Cosmande Beur2014">{{cite journal|last1=Cosman|first1=F.|last2=de Beur|first2=S. J.|last3=LeBoff|first3=M. S.|last4=Lewiecki|first4=E. M.|last5=Tanner|first5=B.|last6=Randall|first6=S.|last7=Lindsay|first7=R.|title=Clinician’s Guide to Prevention and Treatment of Osteoporosis|journal=Osteoporosis International|volume=25|issue=10|year=2014|pages=2359–2381|issn=0937-941X|doi=10.1007/s00198-014-2794-2}}</ref>
** Low [[bone mass]] (T-score between −1.0 and −2.5 at the [[femoral neck]] or [[lumbar spine]]) and a 10-year probability of a [[hip fracture]] ≥3 % or a 10-year probability of a major [[osteoporosis]]-related [[fracture]] ≥20 % based on the US adapted WHO algorithm.<ref name="Cosmande Beur2014">{{cite journal|last1=Cosman|first1=F.|last2=de Beur|first2=S. J.|last3=LeBoff|first3=M. S.|last4=Lewiecki|first4=E. M.|last5=Tanner|first5=B.|last6=Randall|first6=S.|last7=Lindsay|first7=R.|title=Clinician’s Guide to Prevention and Treatment of Osteoporosis|journal=Osteoporosis International|volume=25|issue=10|year=2014|pages=2359–2381|issn=0937-941X|doi=10.1007/s00198-014-2794-2}}</ref>
* There is no established [[medical]] or [[surgical]] therapy for juvenile [[osteoporosis]]. In some cases, no treatment may be needed because the condition usually resolves spontaneously. However, early diagnosis of juvenile [[osteoporosis]] is important so that steps can be taken to protect the child’s [[spine]] and other [[bones]] from [[fracture]] until remission occurs. These steps may include [[physical therapy]], using [[crutches]], avoiding unsafe weight-bearing activities, and other supportive care. A well-balanced diet rich in [[calcium]] and [[vitamin D]] is also important. In severe, long-lasting cases of juvenile [[osteoporosis]], [[bisphosphonates]], have been given to children experimentally.<ref name="urlJuvenile Osteoporosis">{{cite web |url=https://www.niams.nih.gov/health_info/bone/Bone_Health/Juvenile/juvenile_osteoporosis.asp |title=Juvenile Osteoporosis |format= |work= |accessdate=}}</ref>


=== Medical therapy options ===
=== Medical therapy options ===
Medications can be classified into<ref name="pmid37130601">{{cite journal| author=Händel MN, Cardoso I, von Bülow C, Rohde JF, Ussing A, Nielsen SM | display-authors=etal| title=Fracture risk reduction and safety by osteoporosis treatment compared with placebo or active comparator in postmenopausal women: systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials. | journal=BMJ | year= 2023 | volume= 381 | issue=  | pages= e068033 | pmid=37130601 | doi=10.1136/bmj-2021-068033 | pmc=10152340 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=37130601  }} </ref><ref name="pmid36592456">{{cite journal| author=Qaseem A, Hicks LA, Etxeandia-Ikobaltzeta I, Shamliyan T, Cooney TG, Clinical Guidelines Committee of the American College of Physicians | display-authors=etal| title=Pharmacologic Treatment of Primary Osteoporosis or Low Bone Mass to Prevent Fractures in Adults: A Living Clinical Guideline From the American College of Physicians. | journal=Ann Intern Med | year= 2023 | volume= 176 | issue= 2 | pages= 224-238 | pmid=36592456 | doi=10.7326/M22-1034 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=36592456  }} </ref>:
* antiresorptive drugs (selective estrogen receptor modulators, bisphosphonates, and denosumab)
* anabolic treatments (romosozumab and parathyroid hormone receptor agonists)
'''1 Stage 1 - Osteoporosis'''
'''1 Stage 1 - Osteoporosis'''
* 1.'''Improving bone mineral density (BMD)'''
* 1.1&nbsp;'''Improving bone mineral density (BMD)'''
** 1.1.'''Adult'''
** 1.1.1&nbsp;'''Adult'''
*** Preferred regimen (1): Alendronate 70 mg PO weekly 
*** Preferred regimen (1):&nbsp;[[Alendronate]]&nbsp;70 mg [[per os|PO]] weekly&nbsp;
*** Preferred regimen (2): Risedronate 35 mg PO weekly OR 150 mg PO monthly
*** Preferred regimen (2):&nbsp;[[Risedronate]]&nbsp;35 mg [[per os|PO]] weekly OR 150 mg [[per os|PO]] monthly
*** Preferred regimen (3): Ibandronate 150 mg PO monthly OR 3 mg IV every 3 months
*** Preferred regimen (3):&nbsp;[[Ibandronate]]&nbsp;150 mg [[per os|PO]] monthly OR 3 mg [[IV]] every 3 months
*** Preferred regimen (4): Zoledronic acid 5 mg IV annually  
*** Preferred regimen (4):&nbsp;[[Zoledronic acid]] 5 mg [[IV]] annually  
*** Alternative regimen (1): Raloxifen 60 mg PO daily
*** Alternative regimen (1):&nbsp;[[Raloxifene]]&nbsp;60 mg [[per os|PO]] daily
*** Alternative regimen (2): Denosumab 60 mg SC every 6 months
*** Alternative regimen (2):&nbsp;[[Denosumab]]&nbsp;60 mg [[subcutaneous|SC]] every 6 months
*** Alternative regimen (3): Romosozumab 210 mg SC monthly
*** Alternative regimen (3):&nbsp;Romosozumab&nbsp;210 mg [[subcutaneous|SC]] monthly
*** Alternative regimen (4): Teriparatide 20 mcg SC daily, approved for less than 2 years use
*** Alternative regimen (4):&nbsp;[[Teriparatide]] 20 mcg [[subcutaneous|SC]] daily, approved for less than 2 years use
*** Alternative regimen (5): Abaloparatide 80 mcg SC daily, approved for less than 2 years use
*** Alternative regimen (5):&nbsp;Abaloparatide 80 mcg [[subcutaneous|SC]] daily, approved for less than 2 years use
*** Alternative regimen (3): Calcitonin 100 units SC daily OR 200 units intranasal daily
*** Alternative regimen (6):&nbsp;[[Calcitonin]] 100 units [[subcutaneous|SC]] daily OR 200 units intranasal daily


==== Anti-fracture efficacy of approved treatments for postmenopausal women with osteoporosis when given with calcium and vitamin D<ref name="pmid25182228" /> ====
==== Anti-fracture efficacy of approved treatments for postmenopausal women with osteoporosis when given with calcium and vitamin D<ref name="pmid25182228" /> ====
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|Highly effective
|Highly effective
|}
|}
'''1 Stage 1 - Osteoporosis'''
* 1.1&nbsp;'''Improving bone mineral density (BMD)'''
** 1.1.2&nbsp;'''Children and Adolescent'''
** Doses are under studying and evaluation.
*** Preferred regimen (1):&nbsp;[[Alendronate]]&nbsp; weekly&nbsp;
*** Preferred regimen (2):&nbsp;[[Risedronate]]&nbsp;weekly OR monthly
*** Preferred regimen (3):&nbsp;[[Ibandronate]]&nbsp; monthly OR  every 3 months
*** Alternative regimen (1):&nbsp;[[Zoledronic acid]] annually
* Treatment options for children with low bone mass and [[fractures]] are more limited than in adults, underscoring the importance of accurate [[skeletal]] assessments. General measures to address [[skeletal]] risk factors are safe and appropriate first steps for all patients. All strategies to optimize [[bone]] health should be considered. [[Calcium]] intake should meet current recommendations of :
** 500 mg for children 1 to 3 years of age, 
** 800 mg for children 4 to 8 years of age, 
** 1300 mg for children and adolescents 9 to 18 years of age. 
* Routine screening of [[vitamin D]] levels is not indicated in healthy youth. However, the adequacy of total body [[vitamin D]] stores should be assessed in youth at risk of [[bone]] fragility by measuring serum concentrations of [[25-hydroxy vitamin D]]. Concentrations of at least '''''20 ng/mL (50 nmol/L''''') have been recommended for healthy children, but some experts aim for a serum [[25-hydroxy vitamin D]] concentration '''''>30 ng/mL''''' in populations at increased risk of [[fracture]]. 
* Weight-bearing activity should be encouraged, and even short periods of high-intensity exercise (eg, jumping 10 minutes/ day, 3 times/week) have produced measurable gains in [[bone mass]]. The childhood and teenage years appear to be of particular importance for [[bone]] accretion. The Iowa Bone Development Study (a prospective cohort study) showed 10% to 16% greater hip BMC and 8% greater hip areal [[Bone mineral density|BMD]] in participants who accumulated the greatest amount of activity from childhood through adolescence (12-year follow-up).<ref name="JanzLetuchy2014">{{cite journal|last1=Janz|first1=Kathleen F.|last2=Letuchy|first2=Elena M.|last3=Francis|first3=Shelby L.|last4=Metcalf|first4=Kristen M.|last5=Burns|first5=Trudy L.|last6=Levy|first6=Steven M.|title=Objectively Measured Physical Activity Predicts Hip and Spine Bone Mineral Content in Children and Adolescents Ages 5–15 Years: Iowa Bone Development Study|journal=Frontiers in Endocrinology|volume=5|year=2014|issn=1664-2392|doi=10.3389/fendo.2014.00112}}</ref>
*For patients with limited mobility, reducing immobility through [[physical therapy]] or the use of vibrating platforms can be helpful. Reducing inflammation, under-nutrition, or [[hormone]] imbalances  is necessary. In children with [[inflammatory bowel disease]], study showed that a reduction in inflammation through the use of anti–[[Tumor necrosis factor alpha|tumor necrosis factor α]] therapy led to appreciable differences in [[bone]] structure and density. If general measures fail to prevent further [[bone loss]] and [[fracture]], [[pharmacologic]] therapy may be considered. None of the drugs used to treat [[bone]] fragility in the elderly have yet been approved by the [[Food and Drug Administration]] for [[pediatric]] use. Nevertheless, therapy with [[bisphosphonates]] is considered reasonable for children with moderate to severe [[osteogenesis imperfecta]] (2 or more fractures in a year or vertebral compression fractures). For secondary osteoporosis attributable to chronic [[disease]], [[bisphosphonates]] may be used on a compassionate basis to treat low-trauma [[fractures]] of the [[spine]] or [[extremities]]. When [[pharmacologic]] therapy is considered, referral to a specialist with expertise in pediatric bone disorders is advised.<ref name="pmid25919459">{{cite journal |vauthors=Griffin LM, Thayu M, Baldassano RN, DeBoer MD, Zemel BS, Denburg MR, Denson LA, Shults J, Herskovitz R, Long J, Leonard MB |title=Improvements in Bone Density and Structure during Anti-TNF-α Therapy in Pediatric Crohn's Disease |journal=J. Clin. Endocrinol. Metab. |volume=100 |issue=7 |pages=2630–9 |year=2015 |pmid=25919459 |pmc=4490303 |doi=10.1210/jc.2014-4152 |url=}}</ref><ref name="pmid16019729">{{cite journal |vauthors=Rauch F, Glorieux FH |title=Bisphosphonate treatment in osteogenesis imperfecta: which drug, for whom, for how long? |journal=Ann. Med. |volume=37 |issue=4 |pages=295–302 |year=2005 |pmid=16019729 |doi=10.1080/07853890510007386 |url=}}</ref>


'''2 Stage 2 - Glucocorticoid induced osteoporosis'''
'''2 Stage 2 - Glucocorticoid induced osteoporosis'''
* 2.'''Improving bone mineral density (BMD)'''
* 2.1&nbsp;'''Improving bone mineral density (BMD)'''
** 2.1.'''Adult'''
** 2.1.1&nbsp;'''Adult'''
*** Preferred regimen (1): Alendronate 70 mg PO weekly 
*** Preferred regimen (1):&nbsp;[[Alendronate]]&nbsp;70 mg [[per os|PO]] weekly&nbsp;
*** Preferred regimen (2): Risedronate 35 mg PO weekly OR 150 mg PO monthly
*** Preferred regimen (2):&nbsp;[[Risedronate]]&nbsp;35 mg [[per os|PO]] weekly OR 150 mg [[per os|PO]] monthly
*** Preferred regimen (3): Ibandronate 150 mg PO monthly OR 3 mg IV every 3 months
*** Preferred regimen (3):&nbsp;[[Ibandronate]]&nbsp;150 mg [[per os|PO]] monthly OR 3 mg [[IV]] every 3 months
*** Preferred regimen (4): Zoledronic acid 5 mg IV annually  
*** Preferred regimen (4):&nbsp;[[Zoledronic acid]] 5 mg [[IV]] annually  
*** Alternative regimen (1): Raloxifen 60 mg PO daily
*** Alternative regimen (1):&nbsp;[[Raloxifene]]&nbsp;60 mg [[per os|PO]] daily
*** Alternative regimen (2): Denosumab 60 mg SC every 6 months
*** Alternative regimen (2):&nbsp;[[Denosumab]]&nbsp;60 mg [[subcutaneous|SC]] every 6 months
*** Alternative regimen (3): Romosozumab 210 mg SC monthly
*** Alternative regimen (3):&nbsp;Romosozumab&nbsp;210 mg [[subcutaneous|SC]] monthly
*** Alternative regimen (4): Teriparatide 20 mcg SC daily, approved for less than 2 years use
*** Alternative regimen (4):&nbsp;[[Teriparatide]] 20 mcg [[subcutaneous|SC]] daily, approved for less than 2 years use
*** Alternative regimen (5): Abaloparatide 80 mcg SC daily, approved for less than 2 years use
*** Alternative regimen (5):&nbsp;Abaloparatide 80 mcg [[subcutaneous|SC]] daily, approved for less than 2 years use
*** Alternative regimen (3): Calcitonin 100 units SC daily OR 200 units intranasal daily
*** Alternative regimen (6):&nbsp;[[Calcitonin]] 100 units [[subcutaneous|SC]] daily OR 200 units intranasal daily
 
==== Recommendations for initial treatment for glucocorticoid induced osteoporosis in adults by American College of Rheumatology (ACR), 2017<ref name="BuckleyGuyatt2017">{{cite journal|last1=Buckley|first1=Lenore|last2=Guyatt|first2=Gordon|last3=Fink|first3=Howard A.|last4=Cannon|first4=Michael|last5=Grossman|first5=Jennifer|last6=Hansen|first6=Karen E.|last7=Humphrey|first7=Mary Beth|last8=Lane|first8=Nancy E.|last9=Magrey|first9=Marina|last10=Miller|first10=Marc|last11=Morrison|first11=Lake|last12=Rao|first12=Madhumathi|last13=Robinson|first13=Angela Byun|last14=Saha|first14=Sumona|last15=Wolver|first15=Susan|last16=Bannuru|first16=Raveendhara R.|last17=Vaysbrot|first17=Elizaveta|last18=Osani|first18=Mikala|last19=Turgunbaev|first19=Marat|last20=Miller|first20=Amy S.|last21=McAlindon|first21=Timothy|title=2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis|journal=Arthritis & Rheumatology|volume=69|issue=8|year=2017|pages=1521–1537|issn=23265191|doi=10.1002/art.40137}}</ref> ====


==== Recommendations for initial treatment for prevention of GIOP in adults (women not of child-bearing potential and men) beginning long-term GC treatment<ref name="BuckleyGuyatt2017">{{cite journal|last1=Buckley|first1=Lenore|last2=Guyatt|first2=Gordon|last3=Fink|first3=Howard A.|last4=Cannon|first4=Michael|last5=Grossman|first5=Jennifer|last6=Hansen|first6=Karen E.|last7=Humphrey|first7=Mary Beth|last8=Lane|first8=Nancy E.|last9=Magrey|first9=Marina|last10=Miller|first10=Marc|last11=Morrison|first11=Lake|last12=Rao|first12=Madhumathi|last13=Robinson|first13=Angela Byun|last14=Saha|first14=Sumona|last15=Wolver|first15=Susan|last16=Bannuru|first16=Raveendhara R.|last17=Vaysbrot|first17=Elizaveta|last18=Osani|first18=Mikala|last19=Turgunbaev|first19=Marat|last20=Miller|first20=Amy S.|last21=McAlindon|first21=Timothy|title=2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis|journal=Arthritis & Rheumatology|volume=69|issue=8|year=2017|pages=1521–1537|issn=23265191|doi=10.1002/art.40137}}</ref> ====
{{Family tree/start}}
{{Family tree | | | | | | | A01 | | | | | | | | | | |A01=[[Calcium]] and [[vitamin D]] and life style modification}}
{{Family tree | | | | | | | |!| | | | | | | | | | | }}
{{Family tree | |,|-|-|-|-|-|^|-|-|-|.| | | | | | | }}
{{Family tree | A01 | | | | | | | | A02 | | | | | | |A01=Low risk|A02=Moderate/High risk}}
{{Family tree | |!| | | | | | |,|-|-|^|-|-|.| | | | |}}
{{Family tree |boxstyle=text-align: left; | A01 | | | | | A02 | | | | A03 | | | |A01='''No further treatment'''<br> <br>Monitor with yearly [[fracture]] risk assessment<br>with [[Bone mineral density|BMD]] testing every 2-3 years<br>depending on risk factors|A02='''Age < 40 years'''<br> <br>'''1.''' History of osteoporotic [[fracture]], '''OR'''<br>'''2.''' Z score < -3 at [[hip]] or [[spine]] and <br> prednisolone ≥ 7.5 mg/d, '''OR'''<br>'''3.''' >10%/year loss of [[Bone mineral density|BMD]] at [[hip]] or [[spine]] and <br> prednisolone ≥ 7.5 mg/d, '''OR'''<br>'''4.''' Very high dose [[glucocorticoid]] and > 10 years|A03='''Age ≥ 40 years'''<br> <br>'''1.''' History of osteoporotic [[fracture]], '''OR'''<br>'''2.''' Men > 50 years and [[postmenopausal]] women <br> with a [[Bone mineral density|BMD]] T-score ≤ -2.5, '''OR'''<br>'''3.''' FRAX 10-year risk for major osteoporotic [[fracture]] > 10%, '''OR'''<br>'''4.''' FRAX 10-year risk for hip osteoporotic [[fracture]] > 1%, '''OR'''<br>'''5.''' Very high dose of [[glucocorticoid]]}}
{{Family tree | | | | | | | | |`|-|-|v|-|-|'| | | | |}}
{{Family tree | | | | | | | | |,|-|-|^|-|-|.| | | | |}}
{{Family tree | | | | | | | | A01 | | | | A02 | | | |A01='''Treat with an oral [[bisphosphonate]]'''<br> <br>Second-line therapy: '''[[teriparatide]]''' <br> <br>Other suggested therapies (in order of preference)<br>for high risk woman for whom the previous drugs are not appropriate:<br> <br>[[IV]] [[bisphosphonate]]<br> [[Denosumab]]|A02='''Treat with an oral [[bisphosphonate]]'''<br>Other suggested therapies (in order of preference): <br> <br>[[IV]] [[bisphosphonate]]<br> [[Teriparatide]]<br> [[Denosumab]]<br> [[Raloxifen]] for [[postmenopausal]] women if no other therapy is available}}
 
{{Family tree/end}}
 
==== Effect of approved interventions for glucocorticoid-induced osteoporosis on BMD and fracture risk by National Osteoporosis Guideline Group (NOGG), UK, 2014<ref name="pmid25182228" /> ====
{| border="1" cellpadding="5" cellspacing="0" align="center"
! style="background:#efefef;" |Intervention
! style="background:#efefef;" |Spine BMD
! style="background:#efefef;" |Hip BMD
! style="background:#efefef;" |Vertebral fracture
! style="background:#efefef;" |Non-vertebral fracture
|-
|[[Alendronate|'''Alendronate''']]
|Highly effective
|Highly effective
|Moderately effective
|Not adequately evaluated
|-
|[[Etidronate|'''Etidronate''']]
|Highly effective
|Highly effective
|Highly effective
|Not adequately evaluated
|-
|[[Risedronate|'''Risedronate''']]
|Highly effective
|Highly effective
|Highly effective
|Not adequately evaluated
|-
|[[Zoledronic acid|'''Zoledronic acid''']]
|Highly effective
|Highly effective
|Not adequately evaluated
|Not adequately evaluated
|-
|[[Teriparatide|'''Teriparatide''']]
|Highly effective
|Highly effective
|Highly effective
|Not adequately evaluated
|}


=== '''Bisphosphonates''' ===
=== '''Bisphosphonates''' ===
[[Bisphosphonates]] are the '''''first line''''' treatment for [[osteoporosis]] [[disease]]. They are not indicated in people with severe [[renal function impairment]]; thus, it is important to check [[renal function]] and serum [[creatinine]] before [[prescription]]. These drugs have to taken [[Orally ingested|orally]] with large amount of water, not laying down until two hours following consumption, due to high risk of [[esophagitis]]. Rare but serious side effects may include [[osteonecrosis of the jaw]] and atypical [[femoral]] [[Bone fracture|fractures]].
[[Bisphosphonates]] are the '''''first line''''' treatment for [[osteoporosis]] [[disease]]. They are not indicated in people with severe [[renal function impairment]]; thus, it is important to check [[renal function]] and serum [[creatinine]] before [[prescription]]. These drugs need to be taken [[Orally ingested|orally]] with large amount of water and not laying down until two hours following consumption, due to high risk of [[esophagitis]]. Rare but serious side effects may include [[osteonecrosis of the jaw]] and atypical [[femoral]] [[Bone fracture|fractures]].
* [[Alendronate|'''Alendronate''']]: It is frequently used to treat [[osteoporosis]] in men, [[postmenopausal]] women, and also in [[corticosteroid]]-induced [[osteoporosis]]. Alendronate reduces the incidence of spine and hip fractures by about 50 % over 3 years in patients with a prior vertebral fracture or in patients who have osteoporosis at the hip site. It reduces the incidence of vertebral fractures by 48 % over 3 years in patients without a prior vertebral fracture.<ref name="Cosmande Beur2014" />  
* [[Alendronate|'''Alendronate''']]: It is frequently used to treat [[osteoporosis]] in men, [[postmenopausal]] women, and also in [[corticosteroid]]-induced [[osteoporosis]]. Alendronate reduces the incidence of spine and hip fractures by about 50 % over 3 years in patients with a prior vertebral fracture or in patients who have osteoporosis at the hip site. It reduces the incidence of vertebral fractures by 48 % over 3 years in patients without a prior vertebral fracture.<ref name="Cosmande Beur2014" />  
** The dosing is 70mg weekly per oral.   
** The dosing is 70mg weekly per oral.   
** [[Alendronate]] reduces [[Hip (anatomy)|hip]], [[vertebral]], and non-[[vertebral]] [[Osteoporosis|osteoporotic]] [[fractures]].  
** [[Alendronate]] reduces [[Hip (anatomy)|hip]], [[vertebral]], and non-[[vertebral]] [[Osteoporosis|osteoporotic]] [[fractures]].  
* [[Risedronate|'''Risedronate''']]: It is also used to treat [[Paget's disease]]. [[Risedronate]] decreases the [[Bone loss|bone mass loss]]. Also available in delayed release forms. Risedronate reduces the incidence of vertebral fractures by 41 to 49 % and nonvertebral fractures by 36 % over 3 years, with significant risk reduction occurring within 1 year of treatment in patients with a prior vertebral fracture.<ref name="pmid10527181">{{cite journal |vauthors=Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, Chesnut CH, Brown J, Eriksen EF, Hoseyni MS, Axelrod DW, Miller PD |title=Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group |journal=JAMA |volume=282 |issue=14 |pages=1344–52 |year=1999 |pmid=10527181 |doi= |url=}}</ref>  
* [[Risedronate|'''Risedronate''']]: It is also used to treat [[Paget's disease]]. [[Risedronate]] decreases the [[Bone loss|bone mass loss]]. Also available in delayed release forms. Risendronate reduces the incidence of vertebral fractures by 41 to 49 % and nonvertebral fractures by 36 % over 3 years, with significant risk reduction occurring within 1 year of treatment in patients with a prior vertebral fracture.<ref name="pmid10527181">{{cite journal |vauthors=Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, Chesnut CH, Brown J, Eriksen EF, Hoseyni MS, Axelrod DW, Miller PD |title=Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group |journal=JAMA |volume=282 |issue=14 |pages=1344–52 |year=1999 |pmid=10527181 |doi= |url=}}</ref>  
** The dosing is 35mg weekly or 150mg monthly per oral.  
** The dosing is 35mg weekly or 150mg monthly per oral.  
** [[Risedronate]] reduces [[vertebral]] [[fractures]].
** [[Risedronate]] reduces [[vertebral]] [[fractures]].
* [[Ibandronate|'''Ibandronate''']]: It is used to treat osteoporosis only in [[postmenopausal]] women. Ibandronate reduces the incidence of vertebral fractures by about 50 % over 3 years, but reduction in risk of nonvertebral fracture with ibandronate has not been documented.<ref name="pmid15231010">{{cite journal |vauthors=Chesnut CH, Skag A, Christiansen C, Recker R, Stakkestad JA, Hoiseth A, Felsenberg D, Huss H, Gilbride J, Schimmer RC, Delmas PD |title=Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis |journal=J. Bone Miner. Res. |volume=19 |issue=8 |pages=1241–9 |year=2004 |pmid=15231010 |doi=10.1359/JBMR.040325 |url=}}</ref>  
* [[Ibandronate|'''Ibandronate''']]: It is used to treat osteoporosis only in [[postmenopausal]] women. Ibandronate reduces the incidence of [[vertebral fractures]] by about 50 % over 3 years, but the reduction in risk of non-vertebral fracture with ibandronate has not been documented.<ref name="pmid15231010">{{cite journal |vauthors=Chesnut CH, Skag A, Christiansen C, Recker R, Stakkestad JA, Hoiseth A, Felsenberg D, Huss H, Gilbride J, Schimmer RC, Delmas PD |title=Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis |journal=J. Bone Miner. Res. |volume=19 |issue=8 |pages=1241–9 |year=2004 |pmid=15231010 |doi=10.1359/JBMR.040325 |url=}}</ref>  
** The dosing is 150mg monthly per oral; or 3mg every 3 months through [[Intravenous|intravenous (IV)]] rout.   
** The dosing is 150mg monthly per oral, or 3mg every 3 months through [[Intravenous|intravenous (IV)]] route.   
** Regarding that [[Ibandronate]] only reduced [[vertebral]] [[fractures]] and there is no evidence of non-[[vertebral]] fractures improvement, it is rarely prescribed.  
** Regarding that [[Ibandronate]] only reduced [[vertebral]] [[fractures]] and there is no evidence of non-[[vertebral]] fractures improvement, it is rarely prescribed.  
* [[Zoledronic acid|'''Zoledronic''' '''acid''']]: It is also used for [[bone]] destructions due to [[Paget's disease]], [[multiple myeloma]], and [[metastatic]] [[bone tumors]]. Most potent [[bisphosphonate]] that has a higher risk of [[osteonecrosis of the jaw]]. Zoledronic acid reduces the incidence of vertebral fractures by 70% (with significant reduction at 1 year), hip fractures by 41 %, and nonvertebral fractures by 25 % over 3 years in patients with osteoporosis defined by prevalent vertebral fractures and osteoporosis by BMD of the hip.<ref name="pmid17476007">{{cite journal |vauthors=Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR |title=Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis |journal=N. Engl. J. Med. |volume=356 |issue=18 |pages=1809–22 |year=2007 |pmid=17476007 |doi=10.1056/NEJMoa067312 |url=}}</ref>  
* [[Zoledronic acid|'''Zoledronic''' '''acid''']]: It is also used for [[bone]] destruction due to [[Paget's disease]], [[multiple myeloma]], and [[metastatic]] [[bone tumors]]. Most potent [[bisphosphonate]] that has a higher risk of [[osteonecrosis of the jaw]]. Zoledronic acid reduces the incidence of [[vertebral fractures]] by 70% (with the significant reduction at 1 year), [[hip fractures]] by 41 %, and nonvertebral fractures by 25 % over 3 years in patients with osteoporosis defined by prevalent [[vertebral fractures]] and osteoporosis by BMD of the hip.<ref name="pmid17476007">{{cite journal |vauthors=Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR |title=Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis |journal=N. Engl. J. Med. |volume=356 |issue=18 |pages=1809–22 |year=2007 |pmid=17476007 |doi=10.1056/NEJMoa067312 |url=}}</ref>  
** The dosing is 5mg annually through [[Intravenous therapy|IV]] route.   
** The dosing is 5mg annually through [[Intravenous therapy|IV]] route.   
** [[Zoledronate]] reduces [[hip]], [[vertebral]], and non-[[vertebral]] [[Osteoporosis|osteoporotic]] [[fractures]]. Common [[adverse effects]] are [[flu]]-like symptoms and [[bone]] pain, especially presented with first dose.   
** [[Zoledronate]] reduces [[hip]], [[vertebral]], and non-[[vertebral]] [[Osteoporosis|osteoporotic]] [[fractures]]. Common [[adverse effects]] are [[flu]]-like symptoms and [[bone]] pain, especially presented with the first dose.   
===National Osteoporosis Guideline Group (NOGG) algorithm for long term bisphosphonate therapy monitoring<ref name="pmid25182228">{{cite journal| author=Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S et al.| title=Clinician's Guide to Prevention and Treatment of Osteoporosis. | journal=Osteoporos Int | year= 2014 | volume= 25 | issue= 10 | pages= 2359-81 | pmid=25182228 | doi=10.1007/s00198-014-2794-2 | pmc=4176573 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25182228  }} </ref>===  
===National Osteoporosis Guideline Group (NOGG) algorithm for long term bisphosphonate therapy monitoring<ref name="pmid25182228">{{cite journal| author=Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S et al.| title=Clinician's Guide to Prevention and Treatment of Osteoporosis. | journal=Osteoporos Int | year= 2014 | volume= 25 | issue= 10 | pages= 2359-81 | pmid=25182228 | doi=10.1007/s00198-014-2794-2 | pmc=4176573 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25182228  }} </ref>===
{{Family tree/start}}
<span style="font-size:85%">'''Abbreviations:''' '''FRAX:''' Fracture risk assessment tool</span><ref name="urlwww.sheffield.ac.uk">{{cite web |url=https://www.sheffield.ac.uk/FRAX/tool.jsp |title=www.sheffield.ac.uk |format= |work= |accessdate=}}</ref>{{Family tree/start}}
{{Family tree | | | | | | A01 | | | | | | | | |A01=Advise<br>3 years '''[[zoledronic acid]]'''<br>or<br>5 years '''other [[bisphosphonates]]'''<br> (follow up at 3/12 to discuss treatment issues)}}
{{Family tree | | | | | | A01 | | | | | | | | |A01=Advise<br>3 years '''[[zoledronic acid]]'''<br>or<br>5 years '''other [[bisphosphonates]]'''<br> (follow up at 3/12 to discuss treatment issues)}}
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{{Family tree | | |!| | A01 | | | | | | | | A02 | | |A01=Above NOGG intervention threshold<br>or<br>[[Hip]] [[Bone mineral density|BMD]] T-score ≤ -2.5|A02=Below NOGG intervention threshold<br>or<br>[[Hip]] [[Bone mineral density|BMD]] T-score > -2.5}}
{{Family tree | | |!| | A01 | | | | | | | | A02 | | |A01=Above NOGG intervention threshold<br>or<br>[[Hip]] [[Bone mineral density|BMD]] T-score ≤ -2.5|A02=Below NOGG intervention threshold<br>or<br>[[Hip]] [[Bone mineral density|BMD]] T-score > -2.5}}
{{Family tree | | |!| | |!| | | | | | | | | |!| | | |}}
{{Family tree | | |!| | |!| | | | | | | | | |!| | | |}}
{{Family tree | | |`|-| A01 | | | | | | | | A02 | | |A01=1. Check adherence<br>2. Exclude secondary cause<br>3. Re-evaluate treatment choice<br>4. Continue treatment|A02=1. Consider drug holiday<br>2. Repeat '''FRAX+[[Bone mineral density|BMD]]''' in 1.5-3 years}}
{{Family tree |boxstyle=text-align: left; | | |`|-| A01 | | | | | | | | A02 | | |A01=1. Check adherence<br>2. Exclude secondary cause<br>3. Re-evaluate treatment choice<br>4. Continue treatment|A02=1. Consider drug holiday<br>2. Repeat '''FRAX+[[Bone mineral density|BMD]]''' in 1.5-3 years}}


{{Family tree/end}}
{{Family tree/end}}


==== Receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor ====
==== Receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor ====
* '''[[Denosumab]]:''' Human [[monoclonal antibody]] designed to inhibit [[RANKL]] ([[RANK]] ligand), a [[protein]] that acts as the primary [[Signal (biology)|signal]] for [[bone]] removal. It is used to treat [[Osteoporosis]] in elder men and [[postmenopausal]] women.  
* '''[[Denosumab]]:''' Human [[monoclonal antibody]] designed to inhibit [[RANKL]] ([[RANK]] ligand), a [[protein]] that acts as the primary [[Signal (biology)|signal]] for [[bone]] removal. It is used to treat [[osteoporosis]] in older men and [[postmenopausal]] women.  
** The dosing is 60mg subcutaneous every 6 months.   
** The dosing is 60mg [[subcutaneous]] every 6 months.   
** [[Denosumab]] reduces [[hip]], [[vertebral]], and non-[[vertebral]] [[Osteoporosis|osteoporotic]] [[fractures]].   
** [[Denosumab]] reduces [[hip]], [[vertebral]], and non-[[vertebral]] [[Osteoporosis|osteoporotic]] [[fractures]].   
** The major side effects are [[eczema]] and [[nausea]].<ref name="pmid227768602">{{cite journal |vauthors=McClung MR, Lewiecki EM, Geller ML, Bolognese MA, Peacock M, Weinstein RL, Ding B, Rockabrand E, Wagman RB, Miller PD |title=Effect of denosumab on bone mineral density and biochemical markers of bone turnover: 8-year results of a phase 2 clinical trial |journal=Osteoporos Int |volume=24 |issue=1 |pages=227–35 |year=2013 |pmid=22776860 |pmc=3536967 |doi=10.1007/s00198-012-2052-4 |url=}}</ref>   
** The major side effects are [[eczema]] and [[nausea]].<ref name="pmid227768602">{{cite journal |vauthors=McClung MR, Lewiecki EM, Geller ML, Bolognese MA, Peacock M, Weinstein RL, Ding B, Rockabrand E, Wagman RB, Miller PD |title=Effect of denosumab on bone mineral density and biochemical markers of bone turnover: 8-year results of a phase 2 clinical trial |journal=Osteoporos Int |volume=24 |issue=1 |pages=227–35 |year=2013 |pmid=22776860 |pmc=3536967 |doi=10.1007/s00198-012-2052-4 |url=}}</ref>   
*'''Romosozumab''': Human [[monoclonal antibody]] designed to [[sclerostin]], blocking [[protein]] of canonical [[Wnt signaling pathway|Wnt signaling bone formation pathway.]] It is used to prevent [[Osteoporosis|osteoporotic]] [[fractures]] in [[postmenopausal]] women.  
*'''Romosozumab''': Human [[monoclonal antibody]] designed to inhibit [[sclerostin]], a blocking [[protein]] of canonical [[Wnt signaling pathway|Wnt signaling bone formation pathway.]] It is used to prevent [[Osteoporosis|osteoporotic]] [[fractures]] in [[postmenopausal]] women.  
**The dosing is 210mg [[subcutaneous]] monthly.  
**The dosing is 210mg [[subcutaneous]] monthly.  
**Romosozumab reduces [[vertebral fractures]].<ref name="pmid28064540">{{cite journal |vauthors=Bandeira L, Lewiecki EM, Bilezikian JP |title=Romosozumab for the treatment of osteoporosis |journal=Expert Opin Biol Ther |volume=17 |issue=2 |pages=255–263 |year=2017 |pmid=28064540 |doi=10.1080/14712598.2017.1280455 |url=}}</ref>
**Romosozumab reduces [[vertebral fractures]].<ref name="pmid28064540">{{cite journal |vauthors=Bandeira L, Lewiecki EM, Bilezikian JP |title=Romosozumab for the treatment of osteoporosis |journal=Expert Opin Biol Ther |volume=17 |issue=2 |pages=255–263 |year=2017 |pmid=28064540 |doi=10.1080/14712598.2017.1280455 |url=}}</ref>
Line 193: Line 268:


==== Parathyroid hormone and related peptide analogs ====
==== Parathyroid hormone and related peptide analogs ====
*'''[[Teriparatide]]''': Human [[recombinant]] [[parathyroid hormone]] used to treat [[postmenopausal]] woman with [[osteoporosis]] at high risk of [[fracture]] or to increase [[bone]] mass in men with [[osteoporosis]].  
*'''[[Teriparatide]]''': The human [[recombinant]] [[parathyroid hormone]] used to treat the [[postmenopausal]] women with [[osteoporosis]] at high risk of [[fracture]] or to increase [[bone]] mass in men with [[osteoporosis]].  
*Usually, it is used in patients who cannot tolerate the oral [[bisphosphonates]].
*Usually, it is used in patients who cannot tolerate the oral [[bisphosphonates]].
**It is also approved for [[corticosteroid]] induced [[osteoporosis]].  
**It is also approved for [[corticosteroid]] induced [[osteoporosis]].  
**The dosing is 20mcg [[subcutaneous]] daily, approved for less than 2 years use.  
**The dosing is 20mcg [[subcutaneous]] daily, approved for less than 2 years use.  
**[[Teriparatide]] reduces [[vertebral]] and non-[[vertebral]] [[fractures]], but not reduced [[hip fracture]].  
**[[Teriparatide]] reduces [[vertebral]] and non-[[vertebral]] [[fractures]], but not [[hip fracture]].  
**Common side effects include [[nausea]], [[hypercalcemia]], and [[hypercalciuria]]. However, patients with previous [[radiation therapy]], [[paget's disease]], or young patients should avoid this medication.
**Common side effects include [[nausea]], [[hypercalcemia]], and [[hypercalciuria]]. However, patients with previous [[radiation therapy]], [[paget's disease]], or young patients should avoid this medication.
*'''Abaloparatide''': Human [[recombinant]] [[parathyroid hormone]] used to treat [[postmenopausal]] woman with [[osteoporosis]] at high risk of [[fracture]] or to increase [[bone]] mass in men with [[osteoporosis]].  
*'''Abaloparatide''': The human [[recombinant]] [[parathyroid hormone]] used to treat the [[postmenopausal]] women with [[osteoporosis]] at high risk of [[fracture]] or to increase [[bone]] mass in men with [[osteoporosis]].  
**It has a shorter duration of action than [[teriparatide]].   
**It has a shorter duration of action than [[teriparatide]].   
**The dosing is 80mcg [[subcutaneous]] daily, approved for less than 2 years use.   
**The dosing is 80mcg [[subcutaneous]] daily, approved for less than 2 years use.   
Line 206: Line 281:


==== Calcitonin ====
==== Calcitonin ====
* [[Calcitonin]] is a hormone that inhibit the function of [[osteoclasts]] and result in growing [[bone mass]]. On the other hand, it can stimulate the [[osteoblast]] and also inhibit [[sclerostin]] production.  
* [[Calcitonin]] is a hormone that inhibits the function of [[osteoclasts]] and resulting in growing [[bone mass]]. On the other hand, it can stimulate the [[osteoblast]] and also inhibit [[sclerostin]] production.  
* It is used for [[postmenopausal]] women with [[osteoporosis]].  
* It is used for [[postmenopausal]] women with [[osteoporosis]].  
* The dosing is 100units [[subcutaneous]] daily; or 200units [[Intranasal route|intranasal]] daily.  
* The dosing is 100units [[subcutaneous]] daily; or 200units [[Intranasal route|intranasal]] daily.  
Line 213: Line 288:
=== Non-FDA-approved drugs for osteoporosis ===
=== Non-FDA-approved drugs for osteoporosis ===
Nonapproved agents include:
Nonapproved agents include:
* '''Calcitriol''': This synthetic vitamin D analogue, which promotes calcium absorption, has been approved by the FDA for managing hypocalcemia and metabolic bone disease in renal dialysis patients. It is also approved for use in hypoparathyroidism, both surgical and idiopathic, and pseudohypoparathyroidism. No reliable data demonstrate a reduction of risk for osteoporotic fracture.  
* '''Calcitriol''': This synthetic [[vitamin D]] analog, which promotes [[calcium]] absorption, has been approved by the [[FDA]] for managing [[hypocalcemia]] and metabolic [[bone]] [[disease]] in renal [[dialysis]] patients. It is also approved for use in [[hypoparathyroidism]], both surgical and [[idiopathic]], and [[pseudohypoparathyroidism]]. No reliable data demonstrate a reduction of risk for osteoporotic [[fracture]].  
* '''Genistein''': An isoflavone phytoestrogen which is the main ingredient in the prescription “medical food” product Fosteum® and generally regarded as safe by the FDA. Genistein may benefit bone health in postmenopausal women but more data are needed to fully understand its effects on bone health and fracture risk.  
* '''Genistein''': An [[isoflavone]] [[phytoestrogen]] which is the main ingredient in the prescription “medical food” product Fosteum® and generally regarded as safe by the FDA. [[Genistein]] may benefit [[bone]] health in [[postmenopausal]] women but more data are needed to fully understand its effects on [[bone]] health and [[fracture]] risk.  
* '''Other bisphosphonates (etidronate, pamidronate, tiludronate)''': These medications vary chemically from alendronate, ibandronate, risedronate, and zoledronic acid but are in the same drug class. At this time, none is approved for prevention or treatment of osteoporosis. Most of these medications are currently approved for other conditions (e.g., Paget’s disease, hypercalcemia of malignancy, myositis ossificans).  
* '''Other bisphosphonates (etidronate, pamidronate, tiludronate)''': These medications vary chemically from [[alendronate]], [[ibandronate]], [[risedronate]], and [[zoledronic acid]] but are in the same drug class. At this time, none is approved for prevention or treatment of [[osteoporosis]]. Most of these medications are currently approved for other conditions (e.g., [[Paget’s disease]], [[hypercalcemia]] of [[malignancy]], [[myositis ossificans]]).  
* '''PTH (1-84)''': This medication is approved in some countries in Europe for treatment of osteoporosis in women. In one clinical study, PTH(1-84) effectively reduced the risk of vertebral fractures at a dose of 100 mcg/ day.  
* '''PTH (1-84)''': This [[medication]] is approved in some countries in Europe for treatment of [[osteoporosis]] in women. In one clinical study, [[PTH]] (1-84) effectively reduced the risk of [[vertebral fractures]] at a dose of 100 mcg/ day.  
* '''Sodium fluoride''': Through a process that is still unclear, sodium fluoride stimulates the formation of new bone. The quality of bone mass thus developed is uncertain, and the evidence that fluoride reduces fracture risk is conflicting and controversial.  
* '''Sodium fluoride''': Through a process that is still unclear, [[sodium fluoride]] stimulates the formation of new [[bone]]. The quality of [[bone mass]] thus developed is uncertain, and the evidence that [[fluoride]] reduces [[fracture]] risk is conflicting and controversial.  
* '''Strontium ranelate''': This medication is approved for the treatment of osteoporosis in some countries in Europe. Strontium ranelate reduces the risk of both spine and nonvertebral fractures, but the mechanism is unclear. Incorporation of strontium into the crystal structure replacing calciummay be part of itsmechanism of effect. These effects have only been documented with the pharmaceutical grade agent produced by Servier. This effect has not been studied in nutritional supplements containing strontium salts.  
* '''Strontium ranelate''': This medication is approved for the treatment of [[osteoporosis]] in some countries in Europe. [[Strontium ranelate]] reduces the risk of both [[spine]] and nonvertebral [[fractures]], but the mechanism is unclear. Incorporation of [[strontium]] into the crystal structure replacing [[calcium]] may be part of its mechanism of effect. These effects have only been documented with the [[pharmaceutical]] grade agent produced by [[Servier Laboratories|Servier]]. This effect has not been studied in nutritional supplements containing [[strontium]] salts.  
* '''Tibolone''': Tibolone is a tissue-specific, estrogen-like agent that may prevent bone loss and reduce menopausal symptoms. It is indicated in Europe for the treatment of vasomotor symptoms of menopause and for prevention of osteoporosis, but it is not approved for use in the USA.<ref name="Cosmande Beur2014" />
* '''Tibolone''': [[Tibolone]] is a tissue-specific, [[estrogen]]-like agent that may prevent [[bone loss]] and reduce [[menopausal]] symptoms. It is indicated in Europe for the treatment of [[vasomotor]] symptoms of [[menopause]] and for prevention of [[osteoporosis]], but it is not approved for use in the USA.<ref name="Cosmande Beur2014" />


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
{{WS}}
{{WH}}


[[Category:Medicine]]
[[Category:Endocrinology]]
[[Category:Endocrinology]]
[[Category:Radiology]]
[[Category:Up-To-Date]]
[[Category:Orthopedics]]
[[Category:Primary care]]

Latest revision as of 22:47, 6 May 2023

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Eiman Ghaffarpasand, M.D. [2]

Overview

The mainstay of treatment in primary osteoporosis is based on life style modifications. Most of the time in high risk patients and people with past history of osteoporotic fracture, medical therapy is necessary. Bisphosphonates are the first line treatment for osteoporosis. Raloxifene is the second line treatment of osteoporosis in postmenopausal women, for both treatment and prevention. Denosumab is a human monoclonal antibody designed to inhibit RANKL (RANK ligand), a protein that acts as the primary signal for bone removal. It is used to treat osteoporosis in older men and postmenopausal women. Teriparatide and Abaloparatide are human recombinant parathyroid hormones used to treat postmenopausal osteoporosis in women with high risk of fracture or to increase bone mass in men with osteoporosis.

Medical therapy

Fracture prevention medical therapy algorithm[1]

 
 
 
Strategies to prevent fractures and falls

Recommend:
• Dietary calcium 1200 mg/day

Suggest:
Vitamin D (≥ 800–2000 IU/day)
Calcium supplement≤ 500 mg, if dietary calcium not met
Hip protectors
• Multifactorial fall-prevention strategies:
1. Exercise (balance, strength and functional training)
2. Medication reviews (e.g., Beers criteria)
3. Assessment of environmental hazards
4. Use of assistive devices
5. Management of urinary incontinence
 
 
 
 
 
Fracture risk assessment
on admission

• Prior hip fracture?
• Prior vertebral fracture?
• More than one prior fracture
(excluding hands, feet, ankles)?
• Recent use of glucocorticoid and prior
fracture (excluding hands, feet, ankles)?
• Assessed as high risk for fracture and
receiving fracture treatment before admission?
Vertebral fracture present?
(if chest radiography ordered,
screen for vertebral fractures)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
If patient has
a fracture, reassess
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
If "yes" to any of the above,
patient is considered as high risk
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Recommend:
Dietary calcium 1200 mg/day
Vitamin D supplements (800–2000 IU/day)
Calcium supplements ≤ 500 mg, if dietary calcium not met
Hip protectors for mobile residents

Suggest:
Exercise program only as part of multifactorial fracture and fall prevention program
 
 
 
 
 
 
Pharmacologic therapy not appropriate
 
No
 
Is patient expected to live > 1 year?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Is CrCl > 30 mL/min?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
 
 
 
 
 
 
Yes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes
 
 
Does patient have dysphagia?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
For patients with CrCl 15–30 mL/min
Recommend:
Denosumab
(60 mg subcutaneously twice yearly)
Remarks:
• Monitor calcium levels, given higher risk of hypocalcemia
Bisphosphonate therapies are not recommended
• Consider referral to specialist
 
 
 
Recommend:
Denosumab
(60 mg subcutaneously twice yearly)
Zoledronic acid
(5 mg IV once yearly)
Suggest:
Teriparatide
(20 mcg subcutaneously daily)
 
 
Recommend:
Alendronate (70 mg weekly)
Risedronate (35 mg weekly or 150 mg monthly)
Denosumab (60 mg subcutaneously twice yearly)
Zoledronic acid (5 mg IV once yearly)
Suggest:
Teriparatide (20 mcg subcutaneously daily)
 
 

Most of the time in high risk patients and people with past history of osteoporotic fracture, medical therapy is necessary.[2]

Medical therapy purpose

Medical therapy candidates

Medical therapy options

Medications can be classified into[8][9]:

  • antiresorptive drugs (selective estrogen receptor modulators, bisphosphonates, and denosumab)
  • anabolic treatments (romosozumab and parathyroid hormone receptor agonists)


1 Stage 1 - Osteoporosis

  • 1.1 Improving bone mineral density (BMD)
    • 1.1.1 Adult
      • Preferred regimen (1): Alendronate 70 mg PO weekly 
      • Preferred regimen (2): Risedronate 35 mg PO weekly OR 150 mg PO monthly
      • Preferred regimen (3): Ibandronate 150 mg PO monthly OR 3 mg IV every 3 months
      • Preferred regimen (4): Zoledronic acid 5 mg IV annually
      • Alternative regimen (1): Raloxifene 60 mg PO daily
      • Alternative regimen (2): Denosumab 60 mg SC every 6 months
      • Alternative regimen (3): Romosozumab 210 mg SC monthly
      • Alternative regimen (4): Teriparatide 20 mcg SC daily, approved for less than 2 years use
      • Alternative regimen (5): Abaloparatide 80 mcg SC daily, approved for less than 2 years use
      • Alternative regimen (6): Calcitonin 100 units SC daily OR 200 units intranasal daily

Anti-fracture efficacy of approved treatments for postmenopausal women with osteoporosis when given with calcium and vitamin D[10]

Vertebral fracture Non-vertebral fracture Hip fracture
Alendronate Highly effective Highly effective Highly effective
Etidronate Highly effective Moderately effective Not adequately evaluated
Ibandronate Highly effective Highly effective Not adequately evaluated
Risedronate Highly effective Highly effective Highly effective
Zoledronic acid Highly effective Highly effective Highly effective
Denosumab Highly effective Highly effective Highly effective
Calcitriol Highly effective Moderately effective Not adequately evaluated
Raloxifene Highly effective Not adequately evaluated Not adequately evaluated
Strontium ranelate Highly effective Highly effective Highly effective
Teriparatide Highly effective Highly effective Not adequately evaluated
Recombinant human PTH (1-84) Highly effective Not adequately evaluated Not adequately evaluated
Hormone replacement therapy (HRT) Highly effective Highly effective Highly effective

1 Stage 1 - Osteoporosis

  • 1.1 Improving bone mineral density (BMD)
    • 1.1.2 Children and Adolescent
    • Doses are under studying and evaluation.
  • Treatment options for children with low bone mass and fractures are more limited than in adults, underscoring the importance of accurate skeletal assessments. General measures to address skeletal risk factors are safe and appropriate first steps for all patients. All strategies to optimize bone health should be considered. Calcium intake should meet current recommendations of :
    • 500 mg for children 1 to 3 years of age,
    • 800 mg for children 4 to 8 years of age,
    • 1300 mg for children and adolescents 9 to 18 years of age.
  • Routine screening of vitamin D levels is not indicated in healthy youth. However, the adequacy of total body vitamin D stores should be assessed in youth at risk of bone fragility by measuring serum concentrations of 25-hydroxy vitamin D. Concentrations of at least 20 ng/mL (50 nmol/L) have been recommended for healthy children, but some experts aim for a serum 25-hydroxy vitamin D concentration >30 ng/mL in populations at increased risk of fracture.
  • Weight-bearing activity should be encouraged, and even short periods of high-intensity exercise (eg, jumping 10 minutes/ day, 3 times/week) have produced measurable gains in bone mass. The childhood and teenage years appear to be of particular importance for bone accretion. The Iowa Bone Development Study (a prospective cohort study) showed 10% to 16% greater hip BMC and 8% greater hip areal BMD in participants who accumulated the greatest amount of activity from childhood through adolescence (12-year follow-up).[11]
  • For patients with limited mobility, reducing immobility through physical therapy or the use of vibrating platforms can be helpful. Reducing inflammation, under-nutrition, or hormone imbalances is necessary. In children with inflammatory bowel disease, study showed that a reduction in inflammation through the use of anti–tumor necrosis factor α therapy led to appreciable differences in bone structure and density. If general measures fail to prevent further bone loss and fracture, pharmacologic therapy may be considered. None of the drugs used to treat bone fragility in the elderly have yet been approved by the Food and Drug Administration for pediatric use. Nevertheless, therapy with bisphosphonates is considered reasonable for children with moderate to severe osteogenesis imperfecta (2 or more fractures in a year or vertebral compression fractures). For secondary osteoporosis attributable to chronic disease, bisphosphonates may be used on a compassionate basis to treat low-trauma fractures of the spine or extremities. When pharmacologic therapy is considered, referral to a specialist with expertise in pediatric bone disorders is advised.[12][13]

2 Stage 2 - Glucocorticoid induced osteoporosis

  • 2.1 Improving bone mineral density (BMD)
    • 2.1.1 Adult
      • Preferred regimen (1): Alendronate 70 mg PO weekly 
      • Preferred regimen (2): Risedronate 35 mg PO weekly OR 150 mg PO monthly
      • Preferred regimen (3): Ibandronate 150 mg PO monthly OR 3 mg IV every 3 months
      • Preferred regimen (4): Zoledronic acid 5 mg IV annually
      • Alternative regimen (1): Raloxifene 60 mg PO daily
      • Alternative regimen (2): Denosumab 60 mg SC every 6 months
      • Alternative regimen (3): Romosozumab 210 mg SC monthly
      • Alternative regimen (4): Teriparatide 20 mcg SC daily, approved for less than 2 years use
      • Alternative regimen (5): Abaloparatide 80 mcg SC daily, approved for less than 2 years use
      • Alternative regimen (6): Calcitonin 100 units SC daily OR 200 units intranasal daily

Recommendations for initial treatment for glucocorticoid induced osteoporosis in adults by American College of Rheumatology (ACR), 2017[14]

 
 
 
 
 
 
Calcium and vitamin D and life style modification
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Low risk
 
 
 
 
 
 
 
Moderate/High risk
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No further treatment

Monitor with yearly fracture risk assessment
with BMD testing every 2-3 years
depending on risk factors
 
 
 
 
Age < 40 years

1. History of osteoporotic fracture, OR
2. Z score < -3 at hip or spine and
prednisolone ≥ 7.5 mg/d, OR
3. >10%/year loss of BMD at hip or spine and
prednisolone ≥ 7.5 mg/d, OR
4. Very high dose glucocorticoid and > 10 years
 
 
 
Age ≥ 40 years

1. History of osteoporotic fracture, OR
2. Men > 50 years and postmenopausal women
with a BMD T-score ≤ -2.5, OR
3. FRAX 10-year risk for major osteoporotic fracture > 10%, OR
4. FRAX 10-year risk for hip osteoporotic fracture > 1%, OR
5. Very high dose of glucocorticoid
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treat with an oral bisphosphonate

Second-line therapy: teriparatide

Other suggested therapies (in order of preference)
for high risk woman for whom the previous drugs are not appropriate:

IV bisphosphonate
Denosumab
 
 
 
Treat with an oral bisphosphonate
Other suggested therapies (in order of preference):

IV bisphosphonate
Teriparatide
Denosumab
Raloxifen for postmenopausal women if no other therapy is available
 
 
 

Effect of approved interventions for glucocorticoid-induced osteoporosis on BMD and fracture risk by National Osteoporosis Guideline Group (NOGG), UK, 2014[10]

Intervention Spine BMD Hip BMD Vertebral fracture Non-vertebral fracture
Alendronate Highly effective Highly effective Moderately effective Not adequately evaluated
Etidronate Highly effective Highly effective Highly effective Not adequately evaluated
Risedronate Highly effective Highly effective Highly effective Not adequately evaluated
Zoledronic acid Highly effective Highly effective Not adequately evaluated Not adequately evaluated
Teriparatide Highly effective Highly effective Highly effective Not adequately evaluated

Bisphosphonates

Bisphosphonates are the first line treatment for osteoporosis disease. They are not indicated in people with severe renal function impairment; thus, it is important to check renal function and serum creatinine before prescription. These drugs need to be taken orally with large amount of water and not laying down until two hours following consumption, due to high risk of esophagitis. Rare but serious side effects may include osteonecrosis of the jaw and atypical femoral fractures.

National Osteoporosis Guideline Group (NOGG) algorithm for long term bisphosphonate therapy monitoring[10]

Abbreviations: FRAX: Fracture risk assessment tool[18]

 
 
 
 
 
Advise
3 years zoledronic acid
or
5 years other bisphosphonates
(follow up at 3/12 to discuss treatment issues)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No fracture
 
 
 
 
 
 
 
Recurrent fracture(s)
Prevalent vertebral fracture(s)

In patients taking oral bisphosphonate consider continuation if:
• Age > 75 years
• Previous hip fracture
• Current oral glucocorticoid therapy ≥ 7.5 mg/d prednisolone
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
FRAX+BMD
after 3 years zoledronic acid
or
5 years other bisphosphonates
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Above NOGG intervention threshold
or
Hip BMD T-score ≤ -2.5
 
 
 
 
 
 
 
Below NOGG intervention threshold
or
Hip BMD T-score > -2.5
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1. Check adherence
2. Exclude secondary cause
3. Re-evaluate treatment choice
4. Continue treatment
 
 
 
 
 
 
 
1. Consider drug holiday
2. Repeat FRAX+BMD in 1.5-3 years
 
 
 
 

Receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor

Selective estrogen receptor modulator (SERM)

Parathyroid hormone and related peptide analogs

Calcitonin

Non-FDA-approved drugs for osteoporosis

Nonapproved agents include:

References

  1. Papaioannou A, Santesso N, Morin SN, Feldman S, Adachi JD, Crilly R, Giangregorio LM, Jaglal S, Josse RG, Kaasalainen S, Katz P, Moser A, Pickard L, Weiler H, Whiting S, Skidmore CJ, Cheung AM (2015). "Recommendations for preventing fracture in long-term care". CMAJ. 187 (15): 1135–44, E450–61. doi:10.1503/cmaj.141331. PMC 4610837. PMID 26370055.
  2. Minisola S, Cipriani C, Occhiuto M, Pepe J (2017). "New anabolic therapies for osteoporosis". Intern Emerg Med. doi:10.1007/s11739-017-1719-4. PMID 28780668.
  3. Cummings SR, Karpf DB, Harris F, Genant HK, Ensrud K, LaCroix AZ, Black DM (2002). "Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs". Am. J. Med. 112 (4): 281–9. PMID 11893367.
  4. 4.0 4.1 4.2 Ensrud KE, Crandall CJ (2017). "Osteoporosis". Ann. Intern. Med. 167 (3): ITC17–ITC32. doi:10.7326/AITC201708010. PMID 28761958.
  5. Bauer DC (2013). "Clinical practice. Calcium supplements and fracture prevention". N. Engl. J. Med. 369 (16): 1537–43. doi:10.1056/NEJMcp1210380. PMC 4038300. PMID 24131178.
  6. 6.0 6.1 6.2 Cosman, F.; de Beur, S. J.; LeBoff, M. S.; Lewiecki, E. M.; Tanner, B.; Randall, S.; Lindsay, R. (2014). "Clinician's Guide to Prevention and Treatment of Osteoporosis". Osteoporosis International. 25 (10): 2359–2381. doi:10.1007/s00198-014-2794-2. ISSN 0937-941X.
  7. "Juvenile Osteoporosis".
  8. Händel MN, Cardoso I, von Bülow C, Rohde JF, Ussing A, Nielsen SM; et al. (2023). "Fracture risk reduction and safety by osteoporosis treatment compared with placebo or active comparator in postmenopausal women: systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials". BMJ. 381: e068033. doi:10.1136/bmj-2021-068033. PMC 10152340 Check |pmc= value (help). PMID 37130601 Check |pmid= value (help).
  9. Qaseem A, Hicks LA, Etxeandia-Ikobaltzeta I, Shamliyan T, Cooney TG, Clinical Guidelines Committee of the American College of Physicians; et al. (2023). "Pharmacologic Treatment of Primary Osteoporosis or Low Bone Mass to Prevent Fractures in Adults: A Living Clinical Guideline From the American College of Physicians". Ann Intern Med. 176 (2): 224–238. doi:10.7326/M22-1034. PMID 36592456 Check |pmid= value (help).
  10. 10.0 10.1 10.2 Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S; et al. (2014). "Clinician's Guide to Prevention and Treatment of Osteoporosis". Osteoporos Int. 25 (10): 2359–81. doi:10.1007/s00198-014-2794-2. PMC 4176573. PMID 25182228.
  11. Janz, Kathleen F.; Letuchy, Elena M.; Francis, Shelby L.; Metcalf, Kristen M.; Burns, Trudy L.; Levy, Steven M. (2014). "Objectively Measured Physical Activity Predicts Hip and Spine Bone Mineral Content in Children and Adolescents Ages 5â€"15 Years: Iowa Bone Development Study". Frontiers in Endocrinology. 5. doi:10.3389/fendo.2014.00112. ISSN 1664-2392.
  12. Griffin LM, Thayu M, Baldassano RN, DeBoer MD, Zemel BS, Denburg MR, Denson LA, Shults J, Herskovitz R, Long J, Leonard MB (2015). "Improvements in Bone Density and Structure during Anti-TNF-α Therapy in Pediatric Crohn's Disease". J. Clin. Endocrinol. Metab. 100 (7): 2630–9. doi:10.1210/jc.2014-4152. PMC 4490303. PMID 25919459.
  13. Rauch F, Glorieux FH (2005). "Bisphosphonate treatment in osteogenesis imperfecta: which drug, for whom, for how long?". Ann. Med. 37 (4): 295–302. doi:10.1080/07853890510007386. PMID 16019729.
  14. Buckley, Lenore; Guyatt, Gordon; Fink, Howard A.; Cannon, Michael; Grossman, Jennifer; Hansen, Karen E.; Humphrey, Mary Beth; Lane, Nancy E.; Magrey, Marina; Miller, Marc; Morrison, Lake; Rao, Madhumathi; Robinson, Angela Byun; Saha, Sumona; Wolver, Susan; Bannuru, Raveendhara R.; Vaysbrot, Elizaveta; Osani, Mikala; Turgunbaev, Marat; Miller, Amy S.; McAlindon, Timothy (2017). "2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis". Arthritis & Rheumatology. 69 (8): 1521–1537. doi:10.1002/art.40137. ISSN 2326-5191.
  15. Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, Chesnut CH, Brown J, Eriksen EF, Hoseyni MS, Axelrod DW, Miller PD (1999). "Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group". JAMA. 282 (14): 1344–52. PMID 10527181.
  16. Chesnut CH, Skag A, Christiansen C, Recker R, Stakkestad JA, Hoiseth A, Felsenberg D, Huss H, Gilbride J, Schimmer RC, Delmas PD (2004). "Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis". J. Bone Miner. Res. 19 (8): 1241–9. doi:10.1359/JBMR.040325. PMID 15231010.
  17. Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR (2007). "Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis". N. Engl. J. Med. 356 (18): 1809–22. doi:10.1056/NEJMoa067312. PMID 17476007.
  18. "www.sheffield.ac.uk".
  19. McClung MR, Lewiecki EM, Geller ML, Bolognese MA, Peacock M, Weinstein RL, Ding B, Rockabrand E, Wagman RB, Miller PD (2013). "Effect of denosumab on bone mineral density and biochemical markers of bone turnover: 8-year results of a phase 2 clinical trial". Osteoporos Int. 24 (1): 227–35. doi:10.1007/s00198-012-2052-4. PMC 3536967. PMID 22776860.
  20. Bandeira L, Lewiecki EM, Bilezikian JP (2017). "Romosozumab for the treatment of osteoporosis". Expert Opin Biol Ther. 17 (2): 255–263. doi:10.1080/14712598.2017.1280455. PMID 28064540.
  21. Lippuner K, Buchard PA, De Geyter C, Imthurn B, Lamy O, Litschgi M, Luzuy F, Schiessl K, Stute P, Birkhäuser M (2012). "Recommendations for raloxifene use in daily clinical practice in the Swiss setting". Eur Spine J. 21 (12): 2407–17. doi:10.1007/s00586-012-2404-y. PMC 3508239. PMID 22739699.
  22. Felsenfeld, A. J.; Levine, B. S. (2015). "Calcitonin, the forgotten hormone: does it deserve to be forgotten?". Clinical Kidney Journal. 8 (2): 180–187. doi:10.1093/ckj/sfv011. ISSN 2048-8505.