Residency · Residency · Family Medicine
Osteoporosis Screening and Fracture Prevention
Introduction
Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration, leading to increased fracture risk. It affects approximately 10 million Americans, with an additional 44 million having low bone density. Family physicians play a central role in screening, risk stratification, treatment initiation, and long-term fracture prevention.
Pathophysiology
Bone is continuously remodeled through a balance of osteoblast (formation) and osteoclast (resorption) activity. Peak bone mass is achieved by age 25 to 30, after which resorption gradually exceeds formation. Estrogen deficiency at menopause accelerates bone loss at a rate of 2 to 3% per year for 5 to 7 years post-menopause. The RANKL-RANK-OPG pathway is the key regulatory system for osteoclast differentiation and activity.
Risk Factors
Non-Modifiable
Non-modifiable risk factors include advanced age (risk doubles each decade after 50), female sex (4:1 female-to-male ratio for osteoporotic fractures), White and Asian ethnicity, family history of hip fracture, and personal history of fragility fracture.
Modifiable
Modifiable risk factors include low body weight (BMI less than 20), smoking and excessive alcohol consumption (more than 3 drinks per day), sedentary lifestyle, and low calcium and vitamin D intake. Glucocorticoid use, defined as more than 5 mg of prednisone daily for more than 3 months, is the most common secondary cause. Other medications that increase risk include aromatase inhibitors, androgen deprivation therapy, long-term PPIs, and SSRIs.
Secondary Causes
Secondary causes include hyperparathyroidism, hyperthyroidism, and Cushing syndrome. Malabsorptive conditions such as celiac disease and inflammatory bowel disease contribute. Rheumatoid arthritis, chronic kidney disease, and hypogonadism in both sexes are additional causes.
Screening Recommendations
The USPSTF recommends DXA screening for all women age 65 and older and for younger postmenopausal women with risk factors. Men age 70 and older, or younger men with risk factors, should also be screened per ACP and Endocrine Society recommendations. The FRAX (Fracture Risk Assessment Tool) estimates 10-year fracture probability in untreated patients with T-scores between -1.0 and -2.5. DXA should be repeated every 2 years during treatment to assess response and every 2 to 5 years if monitoring without treatment.
Diagnosis
DXA Interpretation
The T-score compares patient bone mineral density (BMD) to a young adult reference population. A T-score of -1.0 or greater is normal. Osteopenia is defined as a T-score between -1.0 and -2.5. Osteoporosis is defined as a T-score of -2.5 or lower. Severe osteoporosis is a T-score of -2.5 or lower with an accompanying fragility fracture.
| T-Score | Classification | Management | |
|---|---|---|---|
| ≥ -1.0 | Normal | Lifestyle prevention; rescreen per guidelines | |
| -1.0 to -2.5 | Osteopenia | FRAX assessment; treat if 10-yr hip fracture risk ≥3% or major OP fracture ≥20% | |
| ≤ -2.5 | Osteoporosis | Pharmacotherapy indicated | |
| ≤ -2.5 with fragility fracture | Severe osteoporosis | Pharmacotherapy; consider anabolic agent first | Measurements are taken at the lumbar spine (L1 through L4) and proximal femur (femoral neck and total hip), and the lowest T-score is used for diagnosis. |
FRAX Tool
The FRAX tool estimates the 10-year probability of major osteoporotic fracture and hip fracture. Treatment is recommended when the 10-year hip fracture risk is 3% or greater or the major osteoporotic fracture risk is 20% or greater. The tool has limitations: it does not account for dose-response relationships (such as high-dose glucocorticoids), fall risk, or the number of prior fractures.
Laboratory Workup
Basic workup includes CBC, comprehensive metabolic panel (calcium, albumin, creatinine), 25-hydroxyvitamin D, and TSH. Additional tests to consider include PTH, celiac serologies, 24-hour urine calcium, and serum protein electrophoresis to rule out myeloma. Bone turnover markers such as CTX and P1NP can monitor treatment response but are not diagnostic.
Non-Pharmacologic Management
Calcium intake should be 1,000 to 1,200 mg per day, preferably from dietary sources, with supplements used only if dietary intake is insufficient. Vitamin D at 800 to 1,000 IU daily should target a serum 25(OH)D level of 30 ng/mL or greater. Weight-bearing exercise including walking, jogging, stair climbing, and resistance training for 30 minutes most days is recommended. Fall prevention through home safety assessment, vision correction, medication review (reducing sedatives and anticholinergics), balance training, and physical therapy is essential. Smoking cessation and alcohol moderation complete the non-pharmacologic approach.
Pharmacologic Treatment
Antiresorptive Agents
Bisphosphonates are first-line therapy. Oral options include alendronate 70 mg weekly and risedronate 35 mg weekly. Zoledronic acid 5 mg IV annually is the parenteral option. Oral bisphosphonates must be taken with a full glass of water on an empty stomach, and the patient should remain upright for 30 minutes afterward. A drug holiday should be considered after 5 years of oral therapy or 3 years of IV therapy in moderate-risk patients, while high-risk patients should continue treatment. Denosumab (Prolia) at 60 mg subcutaneously every 6 months inhibits RANKL and does not require renal dose adjustment. Rapid bone loss occurs with discontinuation of denosumab, so transition to a bisphosphonate is necessary if treatment is stopped.
Anabolic Agents
Teriparatide, a PTH analog, is given at 20 mcg subcutaneously daily for up to 2 years. Abaloparatide, a PTHrP analog, is dosed at 80 mcg subcutaneously daily for up to 2 years. Romosozumab, an anti-sclerostin antibody, is given at 210 mg subcutaneously monthly for 12 months and should be followed with antiresorptive therapy. Anabolic agents are reserved for very high-risk patients, including those with severe osteoporosis, multiple fractures, or failure of antiresorptive therapy.
Monitoring and Follow-Up
DXA should be repeated every 1 to 2 years during treatment to assess response. Stable or increasing BMD suggests adequate response. A decline of more than 3 to 5% at the spine or more than 4 to 5% at the hip may indicate treatment failure, poor adherence, or unaddressed secondary causes. Medication adherence should be assessed at every visit, as non-adherence is the leading cause of treatment failure.
Adverse Effects and Safety Concerns
Bisphosphonate-related osteonecrosis of the jaw (ONJ) is rare at osteoporosis doses (1 in 10,000 to 100,000), and a dental evaluation should be performed before starting therapy. Atypical femoral fractures are associated with prolonged bisphosphonate use beyond 5 years, and thigh or groin pain in patients on bisphosphonates warrants imaging. Esophageal irritation with oral bisphosphonates is prevented by proper administration technique. Hypocalcemia can occur with denosumab, and adequate calcium and vitamin D should be ensured before starting.
Key Clinical Pearls
FRAX bridges the treatment gap for patients with osteopenia by identifying those who benefit from pharmacotherapy even without a T-score of -2.5 or below. Fall prevention is fracture prevention: a medication that increases BMD does little good if the patient keeps falling. Denosumab should never be abruptly discontinued without transitioning to a bisphosphonate because rebound vertebral fractures can occur within months. Oral bisphosphonate adherence is poor, with 50% of patients discontinuing within 1 year; barriers should be addressed proactively, and IV zoledronic acid should be considered for non-adherent patients. Secondary causes of osteoporosis should always be evaluated before attributing the condition solely to age or menopause.
References
- US Preventive Services Task Force. (2018). Screening for osteoporosis to prevent fractures: Recommendation statement. JAMA, 319(24), 2521-2531.
- Camacho, P. M., et al. (2020). American Association of Clinical Endocrinologists/American College of Endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis. Endocrine Practice, 26(Suppl 1), 1-46.
- Shoback, D., et al. (2020). Pharmacological management of osteoporosis in postmenopausal women: An Endocrine Society guideline update. Journal of Clinical Endocrinology & Metabolism, 105(3), 587-594.
- Compston, J., et al. (2019). UK clinical guideline for the prevention and treatment of osteoporosis. Archives of Osteoporosis, 14(1), 1-24.