What are the considerations for using denosumab (Prolia) in a patient with sacroiliitis, rheumatoid arthritis, avascular necrosis, and a history of glucocorticoid exposure, who also has impaired renal function?

Denosumab Use in Sacroiliitis with Comorbidities

Denosumab is an appropriate treatment option for this patient's osteoporosis and avascular necrosis, particularly given the renal impairment that contraindicates bisphosphonates, but it will not treat the sacroiliitis itself, which requires separate management with NSAIDs and potentially biologic therapy. 1, 2

Key Advantage in Renal Impairment

• Denosumab does not require dose adjustment for any degree of renal impairment, including eGFR <30 mL/min/1.73 m² or dialysis, which is a critical advantage over bisphosphonates like zoledronic acid that require dose reduction when creatinine clearance is 30-60 mL/min and must be held when <30 mL/min. 1, 2
• The degree of renal impairment has no effect on denosumab pharmacokinetics, eliminating the need for dose adjustment. 2

Efficacy for Glucocorticoid-Induced Osteoporosis in Rheumatic Disease

• Denosumab significantly increases BMD in patients with rheumatic diseases and glucocorticoid-induced osteoporosis (GIOP), even when refractory to previous bisphosphonate therapy, with mean increases of 5.8% in lumbar spine and 1.3% in bilateral hip over 24 months. 3
• In Japanese patients with rheumatoid arthritis, denosumab consistently increased BMD regardless of concomitant glucocorticoid administration. 4
• Denosumab may be particularly beneficial for avascular necrosis-related bone pain, as it has demonstrated efficacy in resolving bone pain and improving vertebral BMD in systemic mastocytosis. 5

Critical Safety Monitoring Requirements

Hypocalcemia Risk (Most Important)

• Hypocalcemia risk is significantly elevated with denosumab (13%) compared to zoledronic acid (6%), and this risk is substantially worse in patients with renal impairment. 1, 2
• Pre-existing hypocalcemia must be corrected before initiating denosumab, and all patients require adequate supplementation with calcium and vitamin D throughout treatment. 2
• Monitor serum calcium levels closely, particularly in the first weeks after administration. 2

Osteonecrosis of the Jaw (ONJ)

• Baseline dental evaluation is mandatory before starting denosumab in patients at high risk, particularly those with planned invasive dental procedures. 1
• ONJ incidence is approximately 1-2% with denosumab 60 mg every 6 months. 1
• Maintain optimal oral hygiene throughout treatment and avoid invasive dental procedures during active treatment when possible. 1
• If invasive dental surgery is necessary, defer denosumab therapy until complete healing is confirmed by the dentist. 1

Infection Risk

• Serious infections including skin infections may occur with denosumab, including those leading to hospitalization. 2
• This risk is compounded in rheumatoid arthritis patients, as RA itself increases serious infection risk more than 2-fold, and glucocorticoid use increases this risk up to 4-fold in a dose-dependent manner. 6
• Advise the patient to seek prompt medical attention if signs or symptoms of infection develop, including cellulitis. 2

Multiple Vertebral Fractures Upon Discontinuation

• If denosumab is discontinued, patients must be transitioned to another antiresorptive agent to prevent multiple vertebral fractures that have been reported following discontinuation. 2

Separate Management of Sacroiliitis

Denosumab has no role in treating sacroiliitis itself, which requires distinct management:

Initial Treatment

• NSAIDs are strongly recommended as first-line pharmacological management for active sacroiliitis, with continuous treatment preferred over on-demand use in active disease. 5
• Consider selective COX-2 inhibitors given the patient's glucocorticoid exposure and associated gastrointestinal risk. 5

Local Glucocorticoid Injection

• For isolated active sacroiliitis despite NSAIDs, locally administered parenteral glucocorticoids into the sacroiliac joint is conditionally recommended. 5
• This procedure should be performed in experienced specialist centers, preferably with imaging guidance (ultrasonography or CT). 5
• This is a conditional recommendation with very low-quality evidence. 5

Biologic Therapy Escalation

• If NSAIDs fail after 1 month of continuous use, treatment with TNF inhibitors or IL-17 inhibitors is strongly recommended. 5
• TNF inhibitors are preferred as first-line biologic agents. 7
• Systemic glucocorticoids for long-term management are strongly recommended against in axial spondyloarthritis. 5

Dosing Regimen

• Standard dosing is denosumab 60 mg subcutaneously every 6 months for osteoporosis management. 1, 2
• In rheumatoid arthritis patients, denosumab 60 mg every 3 months showed better maintenance of bone erosion score suppression compared to every 6 months dosing, though this higher frequency is not standard for osteoporosis. 4

Important Clinical Pitfalls

• Do not use denosumab to treat sacroiliitis—it addresses only the bone health complications from glucocorticoid exposure and avascular necrosis. 5, 4
• Never combine Prolia (denosumab) with XGEVA (also denosumab)—patients receiving Prolia should not receive XGEVA. 2
• In patients with rheumatoid arthritis and renal dysfunction, methotrexate and tofacitinib may need adjustment or avoidance, but this does not affect denosumab use. 8
• Denosumab is particularly effective in anti-cyclic citrullinated peptide (CCP) antibody-positive RA patients for reducing joint destruction progression. 9