Osteoporosis medical therapy

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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 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 osteoporotic fracture, 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 for bone removal. It is used to treat Osteoporosis in elder men and postmenopausal women. Teriparatide and Abaloparatide are human recombinant parathyroid hormones used to treat postmenopausal woman with osteoporosis at 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

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 (3): 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[8]

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 recommended daily intake of 500 mg for children 1 to 3 years of age, 800 mg for children 4 to 8 years of age, and 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 by measuring serum concentrations of 25-hydroxyvitamin 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-hydroxyvitamin 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).[9]
  • For patients with limited mobility, reducing immobility through physical therapy or the use of vibrating platforms can be helpful. Reducing inflammation, undernutrition, or hormone imbalances also 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. 45 When pharmacologic therapy is considered, referral to a specialist with expertise in pediatric bone disorders is advised.[10][11]

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 (3): 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[12]

 
 
 
 
 
 
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[8]

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 have to taken 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 fractures.

National Osteoporosis Guideline Group (NOGG) algorithm for long term bisphosphonate therapy monitoring[8]

 
 
 
 
 
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

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