Osteoporosis laboratory findings
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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
There is a limited role for laboratory tests in the diagnosis of osteoporosis; however, they may be used for differentiating primary versus secondary causes of the disease. Laboratory tests for the diagnosis of osteoporosis include some baseline tests like complete blood count (CBC), serum calcium, phosphate, alkaline phosphatase, and 25-(OH)-vitamin D. There are tests for diagnosing secondary osteoporosis, which include but not limited to 24 hr serum calcium, serum protein electrophoresis, and serum thyroid hormones.
Laboratory findings
There is a limited role for laboratory tests in the diagnosis of osteoporosis; however, they may be used for differentiating primary versus secondary causes of the disease.
| Disease | Electrolyte and Bio-marker Studies | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Complete blood count (CBC) | Serum calcium level | 24-hr serum calcium | Serum phosphate level | Serum alkaline phosphatase level | Serum 25-(OH)-vitamin D level | Serum magnesium level | Serum creatinine level | Serum iron and ferritin level | Liver function tests | Thyroid function tests | Serum parathyroid hormone (PTH) level | Serum Testosterone/gonadotropin level | Urine free cortisol level | Over night dexamethasone suppression test | Serum protein electrophoresis/ Urine protein electrophoresis | Anti-gliadin Anti-endomysial antibodies |
Serum tryptase Urine N-methylhistamine | |
| Postmenopausal osteoporosis | - | - | - | - | ↑ | - | - | - | - | - | - | - | - | - | - | - | - | - |
| Vitamin D deficiency | - | ↓ | ↓ | ↓ | ↑ | ↓ | ↓ | - | - | - | - | ↓ | - | - | - | - | - | - |
| Sickle cell anemia | ↓HGB | - | - | - | ↑ | - | - | - | ↓ | ↑ | - | - | - | - | - | - | - | - |
| Multiple myeloma | ↓HGB | ↑ | ↑ | ↑ | ↑ | - | - | ↑ | ↓ | - | - | - | - | - | - | ↑ IgM | - | - |
| Leukemia/lymphoma | ↑WBC | ↑ | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - |
| Alcoholism | ↓HGB | - | - | - | - | - | - | - | ↓ | ↑ | - | - | - | - | - | - | - | - |
| Aplasia | ↓RBC, ↓WBC, ↓PLT | - | - | - | - | - | - | - | ↓ | ↑ | - | - | - | - | - | - | - | - |
| Malignancy | - | ↑↑↑ | ↑↑↑ | ↑ | ↑ | - | - | ↑ | - | ↑ | - | - | - | - | - | - | - | - |
| Hypophosphatemic rickets | - | ↓↓ | ↓ | ↓ | ↑ | ↓↓ | ↓ | - | - | - | - | - | - | - | - | - | - | - |
| Chronic kidney disease | ↓HGB | ↑↑ | ↑↑ | ↓↓ | - | ↓ | ↑ | ↑↑↑ | ↓ | - | - | - | - | - | - | ↑ Urine protein | - | - |
| Destructive bone diseases (e.g., bone tumors) | - | ↑↑ | ↑↑ | ↑ | ↑↑↑ | - | - | ↓ | - | - | - | - | - | - | - | - | - | - |
| Liver diseases | ↓HGB | - | - | - | - | - | - | - | - | ↑↑ | - | - | - | - | - | - | - | - |
| Hemochromatosis | ↑HCT | - | - | - | - | - | - | ↑ | ↑↑↑ | ↑ | - | - | - | - | - | - | - | - |
| Hyperthyroidism | - | - | ↑ | ↑ | - | - | - | - | - | - | ↑↑ | - | - | - | - | - | - | - |
| Hypoparathyroidism | - | ↓ | ↓ | ↑ | ↓ | - | ↓ | - | - | - | - | ↓↓ | - | - | - | - | - | - |
| Hyperparathyroidism | - | ↑ | ↑ | ↓ | ↑ | - | ↑ | - | - | - | - | ↑↑ | - | - | - | - | - | - |
| Hypogonadism | ↓HGB | - | ↓ | ↓ | - | - | - | - | - | - | - | - | ↓↓ | - | - | - | - | - |
| Hypercortisolism (Cushing's syndrome) | - | - | - | - | - | - | - | - | - | - | - | - | - | ↑↑ | not suppresed | - | - | - |
| Celiac disease | ↓HGB | ↓ | ↓ | ↓ | ↑ | ↓ | ↓ | ↓ | ↓↓ | - | ↓ | - | - | - | - | ↓ Plasma protein | Positive | - |
| Mastocytosis | ↑WBC | ↑ | ↑ | ↑ | - | - | - | ↑ | - | - | - | - | - | - | - | - | - | Positive |
| Group | Test | Result | Osteoporosis related disease |
|---|---|---|---|
| Bone formation markers | Serum osteocalcin[1] | Elevated | Postmenopausal osteoporosis |
| Serum bone–specific alkaline phosphatase[2] | 30 percent reduction | Treatment efficacy, increasing bone mineral density (BMD) and decreasing fracture risk | |
| Serum type 1 procollagen[2] | 30 percent reduction | Treatment efficacy, increasing bone mineral density (BMD) and decreasing fracture risk | |
| Bone resorption markers | Urinary hydroxyproline[3] | Elevated | Postmenopausal osteoporosis |
| Urinary total pyridinoline (PYD)[4] | Elevated | Postmenopausal osteoporosis Higher hip fracture risk | |
| Urinary free deoxypyridinoline (DPD)[5] | Elevated | Higher bone resorption in postmenopausal female Lumbar spine osteoporosis | |
| Tartrate-resistant acid phosphatase 5b[6] | Elevated | More severe osteoporosis in hip | |
| Bone sialoprotein (BSP)[7] | Reduced after antiresorptive medicine | Decrease in bone mass loss Improving lumbar vertebrae BMD | |
| Urinary collagen type 1 cross-linked N-telopeptide (NTX)[8] | Reduced to half | Increase in BMD Decrease in fracture risk | |
| Serum collagen type 1 cross-linked C-telopeptide (CTX)[2] | 30 percent reduction | Treatment efficacy Increasing bone mineral density (BMD) Decreasing fracture risk |
Bone turnover markers
When bone mineral density (BMD) measurements do not provide a clear answer, bone turnover markers can be used in selected cases to assess the fracture risk. The combined use of BMD measurements and bone markers is likely to improve the assessment. Bone turnover markers are not routinely employed in diagnosing osteoporosis. Bone markers have two different types:
Bone formation markers
- Serum osteocalcin: Elevated serum osteocalcin level in postmenopausal women reveal primary osteoporosis, also lower BMD in femoral neck and lumbar vertebrae[1]
- Serum bone–specific alkaline phosphatase: 30 percent reduction may reflect treatment efficacy, increasing bone mineral density (BMD) and decreasing fracture risk[2]
- Serum type 1 procollagen: 30 percent reduction may reflect treatment efficacy, increasing BMD and decreasing fracture risk[2]
Bone resorption markers
- Urinary hydroxyproline: Elevated level is consistent with menopause, therefore, hydroxyproline/osteocalcin ratio is favored for both evaluation and also monitoring of postmenopausal osteoporosis[3]
- Urinary total pyridinoline (PYD): Elevated level may reflect higher bone resorption in postmenopausal female with lumbar spine osteoporosis[4]
- Urinary free deoxypyridinoline (DPD): Elevated levels in postmenopausal female correspond with osteoporosis and higher hip fracture risk[5]
- Tartrate-resistant acid phosphatase 5b: Elevated levels may reflect more severe osteoporosis in hip[6]
- Bone sialoprotein (BSP): Reduced levels after antiresorptive medicines reflect the decrease in bone mass loss and improving lumbar vertebrae BMD[7]
- Urinary collagen type 1 cross-linked N-telopeptide (NTX): Reduced level to half of the original measure may reveal increase in BMD and decrease in fracture risk[8]
- Serum collagen type 1 cross-linked C-telopeptide (CTX): Reduced level of 30 percent may reflect treatment efficacy, increasing bone mineral density (BMD) and decreasing fracture risk[2]
Electrolyte and Biomarker Studies
Complete blood count (CBC)
- Reduced hemoglobin level may reveal sickle cell anemia, multiple myeloma, or alcoholism associated osteoporosis.
- Elevated WBC count may reveal leukemia/lymphoma associated osteoporosis.
- Reduced number of all cell types (RBC, WBC, and platelet) may reveal aplasia associated osteoporosis.
Serum calcium level and/or 24-hr serum calcium
- Severe hypercalcemia may reflect malignancy or hyperparathyroidism associated osteoporosis.
- hypocalcemia may reflect vitamin D deficiency associated osteoporosis.
Serum phosphate level
- Reduced serum phosphate level may reveal hypophosphatemic rickets associated osteoporosis.
- Elevated serum phosphate level may reveal vitamin D deficiency, or chronic kidney disease associated osteoporosis.
Serum alkaline phosphatase level
- Elevated serum alkaline phosphatase level may reveal postmenopausal or destructive bone diseases (e.g., bone tumors) associated osteoporosis.
Serum 25-(OH)-vitamin D level
- A reduced serum 25-(OH)-vitamin D level may reveal vitamin D deficiency associated osteoporosis.
Serum creatinine level
- Elevated serum creatinine level may reflect chronic renal failure, which leads to renal osteodystrophy.
Serum magnesium level
- Reduced magnesium level may reflect vitamin D deficiency associated osteoporosis.
Serum iron and ferritin levels
- Elevated iron and ferritin serum levels may reveal hemochromatosis associated osteoporosis.
Liver function tests (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and bilirubin)
- An elevated level of liver function tests may reflect liver diseases (e.g., alcoholism) associated osteoporosis.
Thyroid function tests
- Reduced thyroid stimulating hormone (TSH) and elevated free thyroxine (T4) may reveal hyperthyroidism associated osteoporosis.
Serum parathyroid hormone (PTH) level
- Elevated Serum parathyroid hormone (PTH) level may reflect hyperparathyroidism associated osteoporosis.
- Reduced Serum parathyroid hormone (PTH) level may reveal decreased bone turnover and also increased BMD, but abnormal bone microstructure and dynamic skeletal indices. The indices (i.e., mineralizing surface (MS) and bone formation rate (BFR)) are decreased in hypoparathyroidism; make them prone to osteopenia.[9]
Testosterone and gonadotropin levels
- Reduced testosterone and gonadotropin levels in men may reveal hypogonadism associated osteoporosis.
Urine free cortisol level
- Elevated urine free cortisol level may reflect hypercortisolism (Cushing's syndrome) associated osteoporosis.
Other bio-markers tests
- Over night dexamethasone suppression test (for identifying cushing's syndrome associated osteoporosis)
- Serum protein electrophoresis (SPEP) and urine protein electrophoresis (for identifying multiple myeloma associated osteoporosis)
- Anti-gliadin and anti-endomysial antibodies (for identifying celiac disease associated osteoporosis)
- Serum tryptase and urine N-methylhistamine (for identifying mastocytosis associated osteoporosis)
Abbreviations: HGB: Hemoglobin, WBC: White blood cell, RBC: Red blood cell, IgM: Immunoglobulin M type
References
- ↑ Jump up to: 1.0 1.1 Singh S, Kumar D, Lal AK (2015). "Serum Osteocalcin as a Diagnostic Biomarker for Primary Osteoporosis in Women". J Clin Diagn Res. 9 (8): RC04–7. doi:10.7860/JCDR/2015/14857.6318. PMC 4576601. PMID 26436008.
- ↑ Jump up to: 2.0 2.1 2.2 2.3 2.4 2.5 Bauer DC, Black DM, Garnero P, Hochberg M, Ott S, Orloff J, Thompson DE, Ewing SK, Delmas PD (2004). "Change in bone turnover and hip, non-spine, and vertebral fracture in alendronate-treated women: the fracture intervention trial". J. Bone Miner. Res. 19 (8): 1250–8. doi:10.1359/JBMR.040512. PMID 15231011.
- ↑ Jump up to: 3.0 3.1 Gnudi S, Ripamonti C, Bonini AM, Pratelli L, Figus E (1990). "The importance of urinary hydroxyproline and serumal osteocalcin in the evaluation of post-menopausal osteoporosis". Ital J Orthop Traumatol. 16 (4): 551–7. PMID 2099937.
- ↑ Jump up to: 4.0 4.1 Delmas PD, Schlemmer A, Gineyts E, Riis B, Christiansen C (1991). "Urinary excretion of pyridinoline crosslinks correlates with bone turnover measured on iliac crest biopsy in patients with vertebral osteoporosis". J Bone Miner Res. 6 (6): 639–44. doi:10.1002/jbmr.5650060615. PMID 1887826.
- ↑ Jump up to: 5.0 5.1 Garnero P, Hausherr E, Chapuy MC, Marcelli C, Grandjean H, Muller C, Cormier C, Bréart G, Meunier PJ, Delmas PD (1996). "Markers of bone resorption predict hip fracture in elderly women: the EPIDOS Prospective Study". J. Bone Miner. Res. 11 (10): 1531–8. doi:10.1002/jbmr.5650111021. PMID 8889854.
- ↑ Jump up to: 6.0 6.1 Bauer DC, Garnero P, Harrison SL, Cauley JA, Eastell R, Ensrud KE, Orwoll E (2009). "Biochemical markers of bone turnover, hip bone loss, and fracture in older men: the MrOS study". J. Bone Miner. Res. 24 (12): 2032–8. doi:10.1359/jbmr.090526. PMID 19453262.
- ↑ Jump up to: 7.0 7.1 Shaarawy M, Hasan M (2001). "Serum bone sialoprotein: a marker of bone resorption in postmenopausal osteoporosis". Scand. J. Clin. Lab. Invest. 61 (7): 513–21. PMID 11763409.
- ↑ Jump up to: 8.0 8.1 Eastell R, Barton I, Hannon RA, Chines A, Garnero P, Delmas PD (2003). "Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate". J. Bone Miner. Res. 18 (6): 1051–6. doi:10.1359/jbmr.2003.18.6.1051. PMID 12817758.
- ↑ Rubin MR, Bilezikian JP (2010). "Hypoparathyroidism: clinical features, skeletal microstructure and parathyroid hormone replacement". Arq Bras Endocrinol Metabol. 54 (2): 220–6. PMC 3702727. PMID 20485912.