What is the first line treatment for a typical patient with osteoporosis?

First-Line Treatment for Osteoporosis

Oral bisphosphonates (alendronate or risedronate) are the mandatory first-line treatment for osteoporosis, based on high-certainty evidence demonstrating significant fracture reduction with a favorable safety profile and low cost. 1, 2, 3

Initial Pharmacologic Treatment

• Start with oral bisphosphonates as first-line therapy for all patients with primary osteoporosis, including postmenopausal women, men, and older adults 1, 2, 3
• Specific dosing options include:
  • Alendronate 70 mg once weekly (preferred) or 10 mg daily 2, 3, 4
  • Risedronate 35 mg once weekly (preferred), 150 mg monthly, or 5 mg daily 2, 3
• Bisphosphonates reduce vertebral fractures by 140 per 1000 patients treated and achieve a 50% reduction in hip fractures and 47-56% reduction in vertebral fractures over 3 years 2, 3
• Generic formulations must be prescribed over brand-name medications when available, as they provide equivalent efficacy at significantly lower cost 1, 3

Mandatory Supplementation

• All patients must receive calcium 1,200 mg daily and vitamin D 800 IU daily, as pharmacologic therapy is significantly less effective without adequate supplementation 3, 5
• Target serum vitamin D level is ≥20 ng/mL 2, 3, 5
• Calcium and vitamin D alone are insufficient for established osteoporosis and must be combined with pharmacologic therapy 3

Second-Line Treatment Options

• Denosumab 60 mg subcutaneously every 6 months is recommended only for patients with contraindications to or intolerance of bisphosphonates 1, 2, 3
• Intravenous zoledronic acid 5 mg annually is preferred over denosumab if oral bisphosphonates are not tolerated, particularly in immunosuppressed patients 3
• Denosumab carries risks of serious infections, hypocalcemia, and severe rebound bone loss if discontinued without transitioning to bisphosphonates 2, 3

Very High-Risk Patients

• Anabolic agents (romosozumab, teriparatide, or abaloparatide) should be considered for very high-risk patients, defined as:
  • Age >74 years 2
  • Multiple prior osteoporotic fractures 2, 3
  • T-score ≤-3.0 2
  • Recent vertebral or hip fracture 2, 3
• Patients initially treated with anabolic agents must transition to an antiresorptive agent after discontinuation to preserve gains and prevent serious rebound multiple vertebral fractures 1, 3, 6

Treatment Duration and Monitoring

• Bisphosphonate therapy should be reassessed after 5 years to determine if continued therapy is warranted 1, 3, 5
• Consider stopping bisphosphonates after 5 years unless high fracture risk persists (history of vertebral fracture, T-score remains ≤-2.5, or ongoing high fracture risk), as prolonged use increases risk of atypical femoral fractures and osteonecrosis of the jaw 1, 2, 3, 5
• Bone density should not be monitored during the initial 5-year treatment period, as bisphosphonates reduce fractures even without BMD increases 3

Essential Lifestyle Modifications

• Weight-bearing and resistance training exercises (squats, push-ups, heel raises) are mandatory for all patients 2, 3, 5
• Smoking cessation is mandatory and alcohol intake should be limited to 1-2 drinks per day 2, 3, 5
• Fall prevention counseling and balance exercises must be provided 1, 2

Safety Profile

• High-certainty evidence demonstrates that bisphosphonates cause no difference in serious adverse events compared to placebo at 2-3 years 1, 3
• Common adverse effects include mild upper GI symptoms, influenza-like symptoms, myalgias, arthralgias, and headaches 3
• Rare but serious adverse effects include osteonecrosis of the jaw and atypical femoral fractures, which increase with prolonged use beyond 5 years 1, 2, 3
• Dental examination and completion of necessary dental work should be performed before starting bisphosphonates to minimize osteonecrosis risk 2

Critical Pitfalls to Avoid

• Do not prescribe calcium and vitamin D alone for established osteoporosis, as this is insufficient and requires pharmacologic therapy 3
• Do not use brand-name medications when generic bisphosphonates are available and equally effective 1, 3
• Do not continue bisphosphonates indefinitely without reassessing fracture risk at 5 years due to increasing harm-to-benefit ratio 1, 3
• Do not stop denosumab without transitioning to bisphosphonates to prevent rebound fractures 3
• Do not use menopausal estrogen therapy, estrogen plus progestogen therapy, or raloxifene as first-line therapy due to unfavorable benefit-harm balance 3

Special Populations

• Men with primary osteoporosis should receive the same treatment algorithm: bisphosphonates first-line, denosumab second-line 2, 3
• For glucocorticoid-induced osteoporosis in very high-risk patients, anabolic agents are conditionally recommended, while high-risk patients should receive denosumab or PTH/PTHrP 2
• In elderly patients (>65 years), heightened attention to drug interactions, polypharmacy effects, renal function (adjust or avoid bisphosphonates if CrCl <35 mL/min), and comorbidities is required 5