What is the recommended dosage of bisphosphonate (e.g. alendronate, risedronate) for osteoporosis prophylaxis in a patient with Myasthenia Gravis taking prednisone 60 mg daily?

Bisphosphonate Dosing for Glucocorticoid-Induced Osteoporosis Prophylaxis

For a patient taking prednisone 60 mg daily, oral bisphosphonates should be initiated immediately at standard osteoporosis treatment doses: alendronate 70 mg once weekly or risedronate 35 mg once weekly, along with calcium 1,000-1,200 mg/day and vitamin D 600-800 IU/day. 1

Rationale for Immediate Treatment

Your patient meets multiple criteria for immediate bisphosphonate therapy:

• Prednisone dose >7.5 mg/day for anticipated duration >3 months - This is the primary threshold that mandates bisphosphonate therapy regardless of bone mineral density 1
• Very high-dose glucocorticoid use (≥30 mg/day prednisone) - The 2017 ACR guidelines specifically recommend oral bisphosphonates for patients ≥30 years receiving initial prednisone doses ≥30 mg/day 1
• Strong evidence base - Bisphosphonates have been shown to prevent glucocorticoid-induced bone loss completely, unlike calcium and vitamin D alone which only partially prevent bone loss 1

Specific Dosing Recommendations

First-Line Oral Bisphosphonates 1

• Alendronate 70 mg once weekly (preferred for cost-effectiveness and safety profile)
• Risedronate 35 mg once weekly (alternative if alendronate not tolerated)

Mandatory Adjunctive Therapy 1

• Calcium: 1,000-1,200 mg/day
• Vitamin D: 600-800 IU/day (target serum level ≥20 ng/ml)

Alternative Options if Oral Bisphosphonates Inappropriate 1

In order of preference:

1. IV bisphosphonates (zoledronic acid 5 mg IV annually or pamidronate 60-90 mg IV monthly)
2. Teriparatide (20 mcg subcutaneous daily)
3. Denosumab (60 mg subcutaneous every 6 months)

Critical Consideration for Myasthenia Gravis

Important caveat: One case report documents exacerbation of myasthenia gravis symptoms with alendronate, with the patient experiencing severe muscle weakness and fatigue on dosing days 2. In that case, switching to IV ibandronate (given every 3 months) resolved the symptoms.

Clinical approach:

• Start with standard oral alendronate or risedronate as first-line 1
• Monitor closely for any worsening of myasthenic symptoms on dosing days 2
• If muscle weakness or fatigue worsens temporally related to bisphosphonate dosing, switch to IV bisphosphonate therapy (zoledronic acid or ibandronate) 2
• Do not withhold bisphosphonate therapy entirely, as the fracture risk from 60 mg daily prednisone far outweighs the potential for symptom exacerbation 1, 3

FRAX Adjustment for High-Dose Glucocorticoids

When calculating fracture risk using FRAX for this patient 1, 4:

• Multiply major osteoporotic fracture risk by 1.15
• Multiply hip fracture risk by 1.2
• However, at prednisone 60 mg/day, treatment is indicated regardless of FRAX score 1

Monitoring and Duration

• Initial BMD testing: Obtain within 6 months of starting glucocorticoids if not already done 1
• Reassessment: Every 1-3 years, with earlier reassessment (within 1 year) given the very high glucocorticoid dose 1
• Treatment duration: Continue bisphosphonates for at least 5 years, then reassess fracture risk 5
• Do not perform routine BMD monitoring during the initial 5-year treatment period 5

Evidence Quality

The recommendation for bisphosphonates in glucocorticoid-induced osteoporosis is supported by:

• High-certainty evidence for vertebral fracture reduction (43% relative risk reduction, NNT=31) 3
• Moderate-certainty evidence for BMD improvement at lumbar spine (3.5% absolute increase) and femoral neck (2.06% absolute increase) 3
• Category IA evidence that bisphosphonates completely prevent glucocorticoid-induced bone loss, superior to calcium and vitamin D alone 1

Common Pitfalls to Avoid

• Do not wait for BMD results before starting bisphosphonates at this prednisone dose - treatment is indicated immediately 1
• Do not use calcium and vitamin D alone - they are insufficient at this glucocorticoid dose 1, 3
• Do not forget calcium and vitamin D supplementation alongside bisphosphonates - both are required 1, 4
• Monitor for myasthenia gravis symptom exacerbation specifically on bisphosphonate dosing days 2