What are the first-line medications for treating osteoporosis?

First-Line Medications for Treating Osteoporosis

Bisphosphonates are the recommended first-line pharmacologic treatment for osteoporosis in both postmenopausal women and men due to their established efficacy in reducing fracture risk, safety profile, and cost-effectiveness. 1, 2

Treatment Algorithm for Osteoporosis

First-Line Treatment: Bisphosphonates

• Oral bisphosphonates are the preferred initial treatment option for most patients with osteoporosis 1, 2
• Options include:
  • Alendronate: 70 mg once weekly or 10 mg daily 3, 4
  • Risedronate: 35 mg weekly, 150 mg monthly, or 5 mg daily 3, 5
  • Zoledronic acid: 5 mg IV annually 1, 3
• Generic bisphosphonates (oral alendronate or IV zoledronic acid) are the most cost-effective options 1
• Bisphosphonates have demonstrated efficacy in reducing vertebral, non-vertebral, and hip fractures in postmenopausal women 1, 6
• For men with osteoporosis, bisphosphonates are also recommended as first-line therapy, although evidence is extrapolated from studies in women 1, 2

Second-Line Treatment

• Denosumab (RANK ligand inhibitor) is recommended as second-line therapy for patients who:
  • Have contraindications to bisphosphonates
  • Experience adverse effects from bisphosphonates
  • Cannot tolerate bisphosphonates 1, 3, 2
• Administered as 60 mg subcutaneously every six months 3, 2

Third-Line/Special Situations

• Anabolic agents (teriparatide, abaloparatide) should be considered for:
  • Patients with very high fracture risk
  • Those who have failed antiresorptive therapy
  • Those with severe osteoporosis 3, 2, 7
• Teriparatide is administered as 20 mcg subcutaneously daily 3, 7
• Patients initially treated with anabolic agents should receive an antiresorptive agent after discontinuation to preserve bone density gains 1, 2

Important Considerations

Duration of Therapy

• Consider stopping bisphosphonate treatment after 5 years unless there is a strong indication for continuation 1, 3
• The decision to discontinue should be based on:
  • Baseline fracture risk
  • Type of medication and its half-life in bone
  • Benefits and harms of discontinuation 1, 2

Supplementation

• All patients should receive adequate calcium (1,000-1,200 mg daily) and vitamin D (600-800 IU daily) as part of fracture prevention 1, 3, 2
• Target serum vitamin D levels of at least 20-30 ng/mL 3, 2

Monitoring

• Bone mineral density monitoring during the 5-year pharmacologic treatment period is not recommended 1, 3

Common Pitfalls and Adverse Effects

Bisphosphonates

• Oral bisphosphonates should be avoided in patients with esophageal emptying disorders or those who cannot sit upright for 30 minutes after taking the medication 1, 5
• IV bisphosphonates are generally not recommended in patients with creatinine clearance less than 30 mL/min 1, 5
• Long-term use may be associated with:
  • Atypical femoral fractures
  • Osteonecrosis of the jaw 1

Denosumab

• Discontinuing denosumab without follow-up bisphosphonate therapy can result in rebound bone loss 3, 2

Teriparatide

• Limited to 2 years of use due to concerns about osteosarcoma in animal studies 7
• May cause orthostatic hypotension; instruct patients to sit or lie down if they feel lightheaded after injection 7

Patient Preferences and Cost Considerations

• Patients typically prefer less frequent dosing and consider effectiveness, adverse effects, and convenience equally important 1
• Out-of-pocket costs are extremely important to patients 1
• Generic bisphosphonates are substantially less expensive than other drug classes 1
• Intravenous formulations may have higher overall treatment costs due to clinic visits and infusion costs 1