Possible beneficial effect of bisphosphonates in osteonecrosis of the knee

Knee Surg Sports Traumatol Arthrosc. 2010 Dec;18(12):1638-44. doi: 10.1007/s00167-010-1106-4. Epub 2010 Apr 8.


Osteonecrosis (ON) in the knee occurs as a localized inflammatory disease in relation to spontaneous or non-traumatic ON. Conservative treatment possibilities are limited, and prognosis appears to be poor; in most cases, ON results in knee arthroplasty. Bisphosphonates are suggested to prevent bone resorption and collapse of necrotic bone. In this observational, prospective study we investigated the effect of bisphosphonate treatment in patients with spontaneous or arthroscopy-induced ON of the knee. Twenty-eight patients with osteonecrotic lesions and bone marrow oedema in the knee were included. In 22 patients (80%), ON was identified after arthroscopic surgery of the knee; six patients were diagnosed with spontaneous ON. Patients were initially given pamidronate 120 mg i.v. divided in 3-4 perfusions over 2 weeks, followed by oral bisphosphonate treatment with alendronate 70 mg weekly for 4-6 months. Bisphosphonate treatment resulted in a rapid pain relief, VAS decreasing from 8.2 ± 1.2 at baseline to 5.02 ± 0.6 after 4-6 weeks (p < 0.001). After 6 months, the VAS decreased by 80% (p < 0.001). At the 6-month follow-up, symptoms had resolved completely in 15 patients out of 28; in 6 patients, minimal symptoms (VAS 1-2) remained. In two patients, treatment effect was unsatisfactory, and surgical intervention was needed (arthroplasty). Bone marrow oedema on MRI resolved completely in 18 patients out of 28 with substantial reduction in the remaining. Furthermore, osteonecrotic area resolved completely or demarcation with sclerotic changes of the necrotic area could be observed. Bisphosphonate treatment in patients with osteonecrosis of the knee was associated with a rapid improvement in pain score and radiological consolidation of the area of osteonecrosis. Further randomized, controlled trials are warranted to confirm the potential beneficial role of bisphosphonates in the treatment of osteonecrosis of the knee.

Level of evidence: observational study, level IV.

MeSH terms

  • Alendronate / therapeutic use*
  • Alkaline Phosphatase / blood
  • Amino Acids / urine
  • Bone Density Conservation Agents / therapeutic use*
  • Bone Marrow Diseases / drug therapy
  • Collagen Type I
  • Diphosphonates / therapeutic use*
  • Edema / drug therapy
  • Humans
  • Knee / pathology*
  • Leg Bones / pathology*
  • Magnetic Resonance Imaging
  • Middle Aged
  • Osteocalcin / blood
  • Osteonecrosis / drug therapy*
  • Osteonecrosis / pathology
  • Pain Measurement
  • Pamidronate
  • Peptide Fragments / urine
  • Peptides
  • Procollagen / urine
  • Prospective Studies


  • Amino Acids
  • Bone Density Conservation Agents
  • Collagen Type I
  • Diphosphonates
  • Peptide Fragments
  • Peptides
  • Procollagen
  • collagen type I trimeric cross-linked peptide
  • Osteocalcin
  • pyridinoline
  • deoxypyridinoline
  • Alkaline Phosphatase
  • Pamidronate
  • Alendronate