What is the management of chronic osteonecrosis (avascular necrosis)?

From the Guidelines

Chronic osteonecrosis should be managed with a first-line treatment of NSAIDs/COXIBs in maximum tolerated and approved dosage for 2−4 weeks, with a possible switch to another NSAID/COXIB if the first does not provide benefit or is not tolerated. This approach is based on the recent expert consensus recommendations for the diagnosis and treatment of chronic non-bacterial osteitis (CNO) in adults, as outlined in the study by E. Winter et al. published in the Annals of the Rheumatic Diseases in 2025 1. The recommended NSAIDs/COXIBs include naproxen 375−1100 mg/day, diclofenac 150 mg/day, indomethacin 150 mg/day, ibuprofen 1800 mg/day, celecoxib 200−400 mg/day, etoricoxib 90 mg/day, piroxicam 20 mg/day, and meloxicam 15 mg/day.

Key considerations in managing chronic osteonecrosis include:

• Evaluating treatment response at 2−4 weeks after initiation, with continuation or switching to another NSAID/COXIB as needed 1
• Considering second-line treatments, such as intravenous bisphosphonates (IVBP) or tumour necrosis factor-α inhibitors (TNFi), for patients with insufficient response to first-line treatment or those with specific risk factors, such as spinal bone lesions or significant accumulated skeletal damage 1
• Using IVBP, such as pamidronate or zoledronate, as a preferred second-line option due to their favourable adverse effects profile and lower costs 1
• Monitoring patients for potential complications, including atypical femoral fractures, osteonecrosis of the jaw, and infection risk, particularly in those receiving TNFi 1

In terms of specific treatment protocols, the study by E. Winter et al. provides guidance on the use of IVBP and TNFi, including:

• Pamidronate intravenously 3× 30 mg on 3 consecutive days, every 3 months, or 45−90 mg every month or every 3 months 1
• Zoledronate intravenously 5 mg, according to symptoms 1
• Infliximab 3−5 mg/kg intravenously at 0,2, and 6 weeks, and henceforth 3−5 mg/kg every 6−8 weeks or subcutaneously 120 mg/2 weeks 1
• Etanercept 50 mg/week, subcutaneously, or adalimumab 40 mg/2 weeks, subcutaneously 1

Overall, the management of chronic osteonecrosis requires a tailored approach that takes into account the individual patient's disease stage, location, and risk factors, as well as their response to treatment and potential complications.

From the Research

Management of Chronic Osteonecrosis

• The management of osteonecrosis can be approached through conservative treatment modalities, including pharmacological management and biophysical modalities 2.
• Pharmacological management options include bisphosphonates, prostaglandin agents, enoxaparin, and statins, which have been shown to decrease pain levels and slow the progression of bone necrosis 2.
• Biophysical modalities such as hyperbaric oxygen, extracorporeal shockwave therapy, and pulsed electromagnetic field therapy have also been shown to delay and partially reverse disease progression 2.
• Bisphosphonates, in particular, have been proven to be effective in obviating the need for surgical intervention in osteonecrosis of the femoral head, with combination therapy showing earlier improvement in pain and functional scores compared to oral alendronate therapy only 3.
• The goal of osteoporosis management, which is often related to osteonecrosis, is to prevent fractures, and several pharmacological agents are available to lower fracture risk, including bisphosphonates, denosumab, and anabolic drugs 4.
• Non-pharmacological management of osteoporosis, including diet, physical exercise, lifestyle, fall prevention, and hip protectors, is also an essential part of preventing fractures 5.
• Intravenous zoledronic acid and oral alendronate have been shown to be effective in treating osteoporosis, with both producing a significant increase in bone mineral density and being well tolerated in patients with osteoporotic, low trauma fractures 6.

Treatment Options

• Bisphosphonates: effective in decreasing pain levels and slowing the progression of bone necrosis 2, 3, 4, 6.
• Prostaglandin agents: shown to improve pain, functional, and radiological outcomes 2.
• Enoxaparin: curbs the progression of osteonecrosis 2.
• Statins: have protective effects on bone in patients taking high-dose corticosteroids 2.
• Biophysical modalities: delay and partially reverse disease progression 2.
• Combination therapy: shows earlier improvement in pain and functional scores compared to oral alendronate therapy only 3.
• Denosumab: potently inhibits osteoclast development and activity, with anti-fracture effects similar to those of bisphosphonates 4.
• Anabolic drugs: stimulate bone formation, with greater anti-fracture efficacy and larger increases in bone density than anti-resorptive drugs 4.