Osteoporosis laboratory findings
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Eiman Ghaffarpasand, M.D. [2];Anum Ijaz M.B.B.S., M.D.[3]
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.
Diagnostic Tests for Primary Osteoporosis
| Description | When should this test be used? | Other considerations | |
|---|---|---|---|
| Laboratory investigations | |||
| Blood testing | • Measure serum calcium, phosphate, alkaline phosphatase, and creatinine levels and assess thyroid function | • Prior to initiating therapy to assess for potential secondary causes of osteoporosis (eg, hyperparathyroidism or chronic liver disease)
• Potential contraindications to treatment when considering pharmacotherapy (eg, kidney dysfunction) in individuals with osteoporosis (if levels were not measured within prior year) |
• Clinical guidelines vary in the extent of testing recommended |
| Test individuals at risk for vitamin D deficiency | • Measure serum 25-hydroxyvitamin D (25[OH]D) level | • When treating individuals at risk for vitamin D deficiency, including those with malabsorption, liver disease, chronic kidney disease, reduced sun exposure, and after gastric bypass surgery | • Routine follow-up (3 mo after initiation of supplementation) is not recommended for those without risk factors for vitamin D deficiency |
| Fracture risk assessment tools | |||
| Fracture Risk Assessment Tool (FRAX) | • All 3 tools predict probability of fracture over 1–10 y (depending on the tool used) based on clinical risk factors (with or without measurement of femoral neck for bone mineral density) | • All 3 tools assess absolute fracture risk in adults who are not currently receiving treatment for osteoporosis
• Most guidelines recommend assessing fracture risk when ≥50 y of age in both postmenopausal females and in males |
• Takes into consideration competing risk of mortality
• Bone mineral density is an optional input variable |
| QFracture (assesses the risk of osteoporotic fracture) | • Bone mineral density is not an input variable | ||
| Garvan Fracture Risk Calculator | • Includes the number of falls and prior fractures
• Bone mineral density is an optional input variable | ||
| Imaging | |||
| Imaging of lateral spine | • Vertebral fracture assessment using conventional radiography or dual-energy x-ray absorptiometry | • To identify the presence of a vertebral fracture in individuals with signs or symptoms of acute vertebral fractures or of occult vertebral fractures (such as height loss and kyphosis) | • A confirmed vertebral fracture on imaging (even if the patient is asymptomatic or it is a remote fracture) is associated with a high fracture risk |
| Dual-energy x-ray absorptiometry(DEXA,DXA) | • Areal bone mineral density assessment is expressed in g/cm²
• Expressed as a T score (SDs above or below peak bone mass) |
• To assess bone mineral density in both postmenopausal females and in males aged ≥50 y as part of the fracture risk assessment or for monitoring the response to osteoporosis therapy | • Patients are considered to have normal bone mass when the T score is ≥–1.0
• Patients are considered to have low bone mass (osteopenia) when the T score is between –1.0 and –2.5 • Patients are considered to have osteoporosis when the T score is ≤–2.5 |
| Trabecular bone score(TBS) | • Unitless texture measure derived from dual-energy x-ray absorptiometry images of the lumbar spine, which are only available when specific software is available for the densitometer | • The trabecular bone score can be entered in the FRAX prediction algorithm to assess fracture risk in adults
• When available on the bone mineral density report, the trabecular bone score is useful in individuals close to the treatment threshold (indicates when the results are most likely to alter clinical management) |
• Adding the trabecular bone score to FRAX improves fracture prediction |
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
- Bone resorption markers
| Group | Test | Result | Outcome |
|---|---|---|---|
| Bone formation markers | Serum osteocalcin[2] | Elevated | |
| Serum bone–specific alkaline phosphatase[3] | 30 percent reduction |
| |
| Serum type 1 procollagen[3] | 30 percent reduction |
| |
| Bone resorption markers | Urinary hydroxyproline[4] | Elevated | |
| Urinary total pyridinoline (PYD)[5] | Elevated |
| |
| Urinary free deoxypyridinoline (DPD)[6] | Elevated |
| |
| Tartrate-resistant acid phosphatase 5b[7] | Elevated |
| |
| Bone sialoprotein (BSP)[8] | Reduced after antiresorptive medicine |
| |
| Urinary collagen type 1 cross-linked N-telopeptide (NTX)[9] | Reduced to half | ||
| Serum collagen type 1 cross-linked C-telopeptide (CTX)[3] | 30 percent reduction |
|
Laboratory Findings for Diagnosis of Secondary Osteoporosis
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 | |
Abbreviations: HGB: Hemoglobin; WBC: White blood cell; RBC: Red blood cell; IgM: Immunoglobulin M type
References
- ↑ Morin SN, Leslie WD, Schousboe JT (September 2025). “Osteoporosis: A Review”. JAMA. 334 (10): 894–907. doi:10.1001/jama.2025.6003. PMID 40587168 Check
|pmid=value (help). - ↑ Singh S, Kumar D, Lal AK (August 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. PMID 26436008.
- ↑ 3.0 3.1 3.2 Bauer DC, Black DM, Garnero P, Hochberg M, Ott S, Orloff J, Thompson DE, Ewing SK, Delmas PD (August 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.
- ↑ Gnudi S, Ripamonti C, Bonini AM, Pratelli L, Figus E (December 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.
- ↑ Delmas PD, Schlemmer A, Gineyts E, Riis B, Christiansen C (June 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.
- ↑ Garnero P, Hausherr E, Chapuy MC, Marcelli C, Grandjean H, Muller C, Cormier C, Bréart G, Meunier PJ, Delmas PD (October 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.
- ↑ Bauer DC, Garnero P, Harrison SL, Cauley JA, Eastell R, Ensrud KE, Orwoll E (December 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. PMC 2791517. PMID 19453262.
- ↑ 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. doi:10.1080/003655101753218274. PMID 11763409.
- ↑ Eastell R, Barton I, Hannon RA, Chines A, Garnero P, Delmas PD (June 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.
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