What are the primary prevention options for osteoporosis in postmenopausal women, particularly those with a high risk of fracture and impaired renal function?

Primary Prevention of Osteoporosis in Postmenopausal Women

For postmenopausal women at high risk of fracture, initiate oral bisphosphonates (alendronate 70 mg weekly or risedronate 35 mg weekly) combined with calcium 1,200 mg daily and vitamin D 800 IU daily, as this represents the most effective primary prevention strategy with proven reduction in vertebral, nonvertebral, and hip fractures. 1, 2

Risk Stratification and Screening

Screen all women aged 65 years and older with DXA scanning of the spine and hip to identify those requiring pharmacologic intervention. 1

• For postmenopausal women under age 65 with risk factors (family history, low body weight, smoking, excessive alcohol use, glucocorticoid use), perform DXA screening earlier 1
• A T-score ≤ -2.5 on DXA confirms osteoporosis diagnosis and warrants immediate pharmacologic treatment 1, 3
• Previous fragility fracture (hip or vertebral) is the strongest predictor of future fracture risk and mandates treatment regardless of bone density 4, 5

First-Line Pharmacologic Treatment

Oral bisphosphonates are the preferred initial therapy based on superior safety profile, extensive clinical experience, proven fracture reduction, and low cost compared to all alternatives. 1, 2

Specific Bisphosphonate Regimens:

• Alendronate 70 mg once weekly (preferred generic formulation) 4, 2
• Risedronate 35 mg once weekly or 150 mg monthly 4, 2
• Zoledronic acid 5 mg IV annually (for patients unable to tolerate oral formulations) 2, 3

Evidence for Bisphosphonates:

• Reduce vertebral fractures by 47-56% over 3 years 1, 2
• Reduce hip fractures by 50% in high-risk patients 2
• Reduce nonvertebral fractures with relative risk 0.83 1
• No difference in serious adverse events compared to placebo in randomized trials 2

Essential Supplementation (All Patients)

All postmenopausal women receiving osteoporosis treatment must take calcium 1,200 mg daily and vitamin D 800 IU daily, as pharmacologic therapy is significantly less effective without adequate supplementation. 4, 2, 3

• Calcium and vitamin D alone are insufficient for fracture prevention in those with established osteoporosis 1
• Optimize intake through diet first, then supplement to reach target doses 1, 6

Lifestyle Modifications (All Patients)

Implement weight-bearing exercise, smoking cessation, alcohol limitation (≤1-2 drinks daily), and fall prevention strategies as these reduce fracture risk independent of pharmacologic therapy. 1, 2, 6

• Weight-bearing or resistance training exercises should be performed regularly 1, 6
• Maintain body weight in recommended range; avoid excessive thinness 1, 6
• Assess and modify home fall risks systematically 4, 6

Special Considerations for Impaired Renal Function

In patients with advanced chronic kidney disease (eGFR <30 mL/min/1.73 m²), bisphosphonates carry significant risk and require specialized management. 7

• Denosumab poses severe hypocalcemia risk in advanced kidney disease and requires expert supervision 7
• Prior to initiating any osteoporosis therapy in advanced CKD, evaluate for chronic kidney disease-mineral bone disorder (CKD-MBD) with intact PTH, serum calcium, 25(OH) vitamin D, and 1,25(OH)₂ vitamin D 7
• Treatment should be supervised by a provider with expertise in CKD-MBD management 7
• Monitor calcium levels closely and ensure adequate supplementation before and during treatment 7

Second-Line Options

For patients with contraindications to or intolerance of bisphosphonates, use denosumab 60 mg subcutaneously every 6 months as second-line therapy. 1, 3, 7

• Denosumab reduces vertebral, nonvertebral, and hip fractures in postmenopausal women 1, 7
• Critical warning: Never discontinue denosumab abruptly, as this causes rebound bone loss and multiple vertebral fractures 3, 7
• If discontinuing denosumab, transition to bisphosphonate therapy to prevent rebound 3
• Avoid in patients on immunosuppressive agents due to lack of safety data 1

Raloxifene is a third-line option only for postmenopausal women who cannot tolerate bisphosphonates or denosumab. 1, 8

• Reduces vertebral fractures (RR 0.61) but lacks proven efficacy for hip fractures 1
• Contraindicated in women with active or past venous thromboembolism 8
• Increases risk of fatal stroke in women with coronary disease 8

Very High-Risk Patients

For postmenopausal women at very high risk (recent vertebral fracture, multiple fractures, or T-score ≤ -3.5), consider anabolic agents (teriparatide or romosozumab) as initial therapy, followed by mandatory transition to bisphosphonate. 1, 4

• Anabolic agents must be followed by antiresorptive therapy to preserve gains and prevent rebound fractures 4
• This approach is conditional due to higher cost and treatment burden 1

Treatment Duration and Monitoring

Treat initially for 5 years with bisphosphonates, then reassess fracture risk to determine if continuation is warranted. 2, 3

• Do not monitor bone density during the initial 5-year treatment period, as this provides no clinical benefit 2, 3
• After 5 years, consider stopping unless strong indications for continuation exist (very high ongoing fracture risk) 2
• Prolonged therapy beyond 5 years may reduce vertebral fractures but increases risk of rare adverse events (osteonecrosis of jaw 0.01-0.3%, atypical femoral fractures) 2

Patient Education Priorities

Educate patients on proper bisphosphonate administration (take on empty stomach with full glass of water, remain upright for 30 minutes), expected duration of therapy, importance of adherence, and necessity of calcium/vitamin D supplementation. 4, 2

• Emphasize that osteoporosis is asymptomatic until fracture occurs, making adherence critical 4
• Discuss realistic expectations: treatment prevents future fractures but does not reverse existing bone loss immediately 4
• Address concerns about rare adverse events in context of substantial fracture risk reduction 2

Common Pitfalls to Avoid

• Never use calcium and vitamin D alone as primary prevention in patients with established osteoporosis (T-score ≤ -2.5) 1
• Never prescribe expensive brand-name medications when generic bisphosphonates are equally effective 2
• Never discontinue denosumab without transitioning to bisphosphonate 3, 7
• Never initiate denosumab in patients with advanced kidney disease without expert consultation and CKD-MBD evaluation 7
• Never use raloxifene in women with thromboembolic history or coronary disease 8