When should bisphosphonates (bone density conservation medications) be ordered for patients?

When to Order Bisphosphonates for Patients

Bisphosphonates should be ordered for patients at moderate-to-high risk of fracture, including those with T-scores ≤-2.5, history of osteoporotic fracture, or those on long-term glucocorticoid therapy. 1

Risk Assessment and Indications

Adults ≥40 Years

Bisphosphonate therapy is indicated for:

• Patients with T-score ≤-2.5 at hip or spine 1
• History of osteoporotic fracture 2, 1
• FRAX 10-year risk for major osteoporotic fracture >10% (with glucocorticoid adjustment if applicable) 2
• Patients on glucocorticoid therapy (≥7.5 mg/day of prednisone or equivalent) for ≥3 months 2
• Postmenopausal women and men >50 years with moderate-to-high fracture risk 2
• Very high-dose glucocorticoid treatment (≥30 mg/day prednisone with cumulative annual dose >5g) 2

Adults <40 Years

Bisphosphonate therapy should be considered for:

• History of osteoporotic fracture 2
• Z-score <-2.3 at hip or spine while on glucocorticoid treatment (≥7.5 mg/day for ≥6 months) 2
• Bone loss ≥10%/year at hip or spine 2
• Very high-dose glucocorticoid treatment 2

Special Populations

• Women of childbearing potential: Only if not planning pregnancy during treatment period and using effective contraception 2
• Organ transplant recipients: Follow age-related recommendations if glomerular filtration rate ≥30 ml/min and no metabolic bone disease 2
• HIV-infected patients: Consider bisphosphonates for those with vitamin D deficiency, phosphate wasting, or evidence of osteomalacia 2

Pre-Treatment Evaluation

Before initiating bisphosphonate therapy:

• Measure serum 25(OH)D levels 1
• Check serum calcium level (corrected for albumin) 1
• Correct vitamin D deficiency prior to starting bisphosphonates to prevent hypocalcemia and maximize efficacy 2
• Complete any necessary dental work before starting therapy to reduce risk of osteonecrosis of the jaw 1, 3
• Assess renal function (contraindicated if creatinine clearance <35 mL/min) 3

Treatment Selection Algorithm

1. First-line: Oral bisphosphonates (alendronate, risedronate) 2, 1

   • Weekly dosing preferred for better adherence

2. If oral bisphosphonates not appropriate (due to GI intolerance, adherence concerns, or absorption issues):

   • IV bisphosphonates (zoledronic acid annually or ibandronate quarterly) 2, 1

3. If bisphosphonates contraindicated:

   • Teriparatide for very high fracture risk 2, 1
   • Denosumab (60mg subcutaneous every 6 months) 2, 1
   • Raloxifene for postmenopausal women only (if no history of venous thromboembolism) 2

Follow-up and Monitoring

• DEXA scan 1-2 years after initiating therapy to assess response 1
• Consider treatment failure if fracture occurs after ≥18 months of oral bisphosphonate or bone mineral density loss ≥10%/year 2
• For treatment failure, switch to another class of osteoporosis medication (teriparatide or denosumab) 2

Duration of Treatment

• After 5 years of oral bisphosphonate treatment, assess continued fracture risk 2, 4
• For moderate-to-high risk patients who continue glucocorticoid treatment, continue bisphosphonate therapy beyond 5 years 2
• For low-risk patients who discontinue glucocorticoid treatment, consider discontinuing bisphosphonate but continue calcium and vitamin D 2
• Consider a "drug holiday" after 5-10 years based on fracture risk assessment 4

Important Caveats and Potential Adverse Effects

• Osteonecrosis of jaw: Risk factors include invasive dental procedures, cancer, chemotherapy, poor oral hygiene 3
• Atypical femur fractures: Rare but serious complication with long-term use 3, 4
• GI side effects: Esophageal irritation with oral formulations 3
• Renal impairment: Avoid in patients with creatinine clearance <35 mL/min 3
• Acute phase reactions: More common with IV formulations 3

Bisphosphonates remain the first-line therapy for osteoporosis prevention and treatment due to their proven efficacy in reducing fracture risk, with benefits substantially outweighing potential risks in appropriately selected patients 5, 6.