Bisphosphonate combination therapy for non-femoral avascular necrosis

J Orthop Surg Res. 2019 Apr 24;14(1):112. doi: 10.1186/s13018-019-1152-7.


Background: Avascular necrosis at sites other than femoral head (AVNOFH)/Non-Femoral AVN is a rare entity. No standard of treatment still exists for treating early stages of AVNOFH with most of the cases eventually progressing to a late arthritic stage needing surgical intervention. Bisphosphonates have been shown to prevent disease progression, bone collapse, and the requirement for surgery in avascular necrosis of femoral head. The present study is conducted to evaluate the response of bisphosphonates in the non-surgical management of the early stages of AVNOFH.

Materials and methods: Prospectively collected data of 20 patients diagnosed with an early stage of AVNOFH and treated with the combination of oral alendronate 70 mg weekly and intravenous zolendronic acid (ZA) for 1 year, between Jan 2009 to Dec 2015, was evaluated retrospectively. Clinical evaluation was done using the visual analogue scale (VAS), mean analgesic requirement, and range of motion. Radiographs and magnetic resonance imaging (MRI) were taken to classify the stage of AVN, monitor radiological collapse, and evaluate radiological progression and bone marrow edema changes.

Results: In our analysis of 18 patients (2 lost to follow-up), 5 patients had AVN of the humeral head, 4 patients of the talus, 3 of the lunate, and 2 each of the scaphoid, medial tibial plateau, and second metatarsal head. Pain relief with the drop in VAS score was seen at a mean duration of 4.3 weeks (range 3-13 weeks) after the start of therapy. A 50% reduction in mean analgesic requirement was achieved in the first 6 weeks (2-11 weeks). MRI showed complete resolution of BME in 13 patients at 6 months and in 17 patients (94.4%) at 1 year. Radiological collapse was seen in 6 out of 18 patients at a mean follow-up of 35.3 months (range 14-56 months). Only one out of 18 patients enrolled required surgery.

Conclusion: A combination of oral alendronate and intravenous zolendronic acid provides a pragmatic solution to this rare entity of AVNOFH, where no standard treatment exists.

Keywords: AVN; Avascular necrosis other than femoral head; Bisphosphonates; Bone marrow edema; Osteonecrosis; VAS score.

MeSH terms

  • Administration, Intravenous
  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Alendronate / administration & dosage*
  • Bone Density Conservation Agents / administration & dosage*
  • Diphosphonates / administration & dosage*
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Osteonecrosis / diagnostic imaging*
  • Osteonecrosis / drug therapy*
  • Prospective Studies
  • Young Adult
  • Zoledronic Acid / administration & dosage*


  • Bone Density Conservation Agents
  • Diphosphonates
  • Zoledronic Acid
  • Alendronate