In a patient with Myasthenia Gravis (MG) on Prednisone (generic name: Prednisone) 60 mg daily, when do you start Pneumocystis jirovecii pneumonia (PCP) and osteoporosis prophylaxis and what medications do you use?

Osteoporosis and PCP Prophylaxis in Myasthenia Gravis Patients on High-Dose Prednisone

Start both osteoporosis and PCP prophylaxis immediately when initiating prednisone 60 mg daily in an MG patient, as this dose exceeds all guideline thresholds for prophylaxis.

Osteoporosis Prophylaxis

When to Start

• Begin osteoporosis prophylaxis at treatment initiation when the expected duration of prednisone is ≥3 months 1
• At 60 mg daily prednisone, this patient meets criteria for "very high fracture risk" (≥30 mg daily for ≥30 days), which dramatically increases vertebral fracture risk 14-fold and hip fracture risk 3-fold 1

What to Give

Calcium and Vitamin D (Universal Baseline):

• Start calcium and vitamin D supplementation immediately at initiation of glucocorticoid treatment 1
• This is recommended for all patients regardless of fracture risk stratification 1

Bisphosphonates (First-Line for Most Patients):

• For adults ≥40 years at very high fracture risk (prednisone ≥30 mg daily for ≥30 days): strongly recommend oral bisphosphonates over no treatment 1
• Preferred agents include alendronate or risedronate 1
• The American College of Rheumatology conditionally recommends PTH/PTHrP over anti-resorptive agents for very high-risk patients, but strongly recommends oral bisphosphonates as a minimum intervention 1

For Younger Patients (<40 years):

• If the patient is <40 years receiving high-dose glucocorticoids (≥30 mg daily for ≥30 days), conditionally recommend oral or IV bisphosphonates, PTH/PTHrP, or denosumab 1
• Avoid raloxifene and romosozumab in this age group 1

Clinical Context for MG Patients

• Research suggests MG patients on chronic prednisone may have lower fracture rates than expected, possibly due to effective prophylaxis implementation 2, 3
• One study found only 11.5% osteoporosis rate in female MG patients on long-term prednisone with prophylactic medication, lower than the general Japanese population rate of 22.6% 3
• This reinforces the importance of prophylaxis rather than suggesting it can be omitted

PCP Prophylaxis

When to Start

• Start PCP prophylaxis immediately when initiating prednisone ≥20 mg daily for an expected duration ≥4 weeks 4, 5
• At 60 mg daily, this patient is well above the threshold and at substantial risk 6, 7
• The National Comprehensive Cancer Network recommends prophylaxis for patients receiving ≥20 mg prednisone daily for ≥4 weeks 5

What to Give

First-Line Agent:

• Trimethoprim-sulfamethoxazole (TMP-SMX) is the preferred prophylactic agent, providing a 91% reduction in PJP occurrence and 83% reduction in PJP-related mortality 4, 5
• Standard prophylactic dosing: TMP-SMX 800/160 mg (double-strength) three times weekly 4
• TMP-SMX offers additional protection against common bacterial infections, listeriosis, nocardiosis, and toxoplasmosis 5

Alternative Agents (if TMP-SMX contraindicated):

• Dapsone 100 mg daily (requires G6PD testing before initiation) 4, 5
• Atovaquone 1500 mg daily 4, 5
• Monthly aerosolized pentamidine 4, 5

Critical Risk Factors in This Patient

• A retrospective study of rheumatic disease patients found 86% of PJP cases occurred in patients receiving ≥20 mg prednisone daily, with 43% mortality 6
• In cancer patients, high-dose corticosteroids (≥25 mg prednisolone daily for ≥4 weeks) are a dominant risk factor for PJP 7
• The combination of high-dose steroids (60 mg) and potential for additional immunosuppression in MG (azathioprine, mycophenolate, rituximab) further elevates risk 8

Common Pitfalls to Avoid

For Osteoporosis:

• Do not wait to assess fracture risk with DEXA scanning before starting calcium/vitamin D supplementation—start immediately 1
• Do not delay bisphosphonate initiation in patients ≥40 years on high-dose steroids; the fracture risk is immediate and substantial 1

For PCP:

• Do not wait for lymphopenia to develop before starting prophylaxis—the steroid dose alone warrants prophylaxis 6, 8
• If the patient is also on rituximab or cyclophosphamide (common in refractory MG), prophylaxis is mandatory regardless of steroid dose and should continue for ≥6 months after the last rituximab dose 5
• Monitor for TMP-SMX interactions if the patient is on other immunosuppressants like methotrexate, as this combination increases cytopenia risk 4
• Always check G6PD levels before using dapsone as an alternative to prevent life-threatening hemolysis 4

Duration of Prophylaxis

Osteoporosis:

• Continue calcium/vitamin D throughout the entire duration of glucocorticoid therapy 1
• Continue bisphosphonates as long as the patient remains on glucocorticoids and meets fracture risk criteria 1

PCP:

• Continue TMP-SMX prophylaxis throughout the entire duration of prednisone ≥20 mg daily 5
• If prednisone is tapered below 20 mg daily and no other immunosuppressants are used, prophylaxis can be discontinued 5
• If rituximab is added at any point, extend prophylaxis for at least 6 months after the last rituximab dose 5