Osteoporosis

Osteoporosis is a skeletal disorder characterized by decreased bone strength and density. Dual-energy x-ray absorptiometry (DXA) is the gold standard test for diagnosis. Laboratory testing is useful in ruling out secondary causes of osteoporosis. Bone turnover marker testing is available but is not the primary method for diagnosing or monitoring osteoporosis.

Diagnosis

Indications for Testing

Bone mineral density (BMD) testing (DXA) is recommended for women ≥65 years, postmenopausal women with risk factors, and men ≥70 years or younger men with risk factors (see Screening for details).

Laboratory Testing

Testing for causes of secondary osteoporosis should be considered
- Serum calcium, phosphorus, magnesium
  - If hypercalcemia present: evaluate for hyperparathyroidism, multiple myeloma, cancer
  - Hypophosphatemia: suggests osteomalacia
- CBC: if anemia present, evaluate for underlying conditions, such as multiple myeloma, cancer, malabsorption
- Renal function testing: for renal disease assessment
- Alkaline phosphatase: evaluate for Paget disease
- 24-hour urine calcium: to detect hypercalciuria
- Serum albumin: malnutrition, malabsorption assessment
- Vitamin D 25(OH)D: for vitamin D deficiency; evaluate patients >50 years for malnutrition, malabsorption, and celiac disease
- Thyroid stimulating hormone (TSH): evaluate for hyperthyroidism
- Liver function tests: evaluate for chronic liver disease
- Testosterone (males): evaluate younger men for hypogonadism
- Parathyroid hormone (PTH) (intact or PTH-related protein [PTHrP]): evaluate for hyperparathyroidism
Testing for bone turnover
- Consider testing at initial diagnosis and at follow-up (Camacho, AACE, 2016; Cosman, National Osteoporosis Foundation [NOF], 2014)
- Higher rates of bone turnover are associated with higher fracture risk

Bone Turnover Markers
Bone Formation Markers	Comments
Serum procollagen type 1 N-terminal propeptide Serum procollagen type 1 C-terminal propeptide	Most frequently used marker of bone formation Expect reduced levels when on antiresorptive therapy
Serum osteocalcin	Limited use in clinical practice due to variability
Serum bone-specific alkaline phosphatase	Expect increased levels with antiresorptive therapies
Bone Resorption Markers
Serum collagen type I cross-linked telopeptide	Most frequently used resorptive marker
Urine or serum N-telopeptide	Fasting AM urine spot is optimal
Urine pyridinoline	Expect reduced levels with antiresorptive therapies Early AM spot urine sample is preferred
Urine deoxypyridinoline	Expect reduced levels with antiresorptive therapies Early AM spot urine sample is preferred
Urine hydroxyproline	Nonspecific marker; also reflects bone formation
HPLC, high-performance liquid chromatography

Imaging Studies

Screening

Recommended Populations to Screen for Osteoporosis
	Women	Women (postmenopausal)	Men
USPSTF, 2018	Women ≥65 years	Postmenopausal women <65 years considered at risk for osteoporosis based on formal risk assessment tool	Men: evidence is insufficient for a recommendation for or against screening in men
NOF, 2014	Women >65 years	Postmenopausal women >50 years with either risk factors or fracture (new or historical adult age fracture)	Men >70 years, or >50 years with risk factors or fracture (new or historical adult age fracture)
ACR, 2017	Women or men on glucocorticoids for 6 months, who are <40 years with risk factors or osteoporotic fracture, or ≥40 years
ACR, American College of Rheumatology; USPSTF, U.S. Preventive Services Task Force Sources: Cosman, NOF, 2014; Buckley, ACR, 2017; USPSTF, 2018

Monitoring

Laboratory testing
- Bone turnover markers may be useful for monitoring therapy response (Camacho, AACE, 2016; Cosman, NOF, 2014)
- Vitamin D 25(OH)D: consider reevaluating for adequate concentrations after supplementation
Imaging studies
- DXA: for monitoring during treatment
- Reevaluate at 1-2 years until stable, then repeat every 1-2 years, or less frequently if clinically indicated (Cosman, NOF, 2014)