Alendronate in the treatment of avascular necrosis of the hip

S. Agarwala, A. Sule, B. U. Pai and V. R. Joshi

P. D. Hinduja National Hospital & Medical Research Centre, Veer Savarkar Marg, Mahim, Mumbai 400 016, India

SIR, Avascular necrosis (AVN) of the bone results from decreased blood supply to the bone, resulting in bone death. The most common site is the head of the femur. AVN is characterized by persistent, often nagging and disabling pain associated with significant reduction in joint movement and mobility. The condition tends to run a progressively downhill course. Medical and surgical management generally aims to improve the blood supply by vasodilators and antiplatelet drugs or by physically drilling holes and bone grafting to restore the blood supply to the avascular area. Eighty-five per cent of patients with symptomatic AVN progress to end-stage disease over a 2-yr period [1]. So far, there is no universally accepted treatment that relieves pain and halts its progression. In this communication we report our early experience with the use of alendronate, a bisphosphonate, in AVN of the hip.

All cases of proven AVN seen by us between February and October 2000 were assessed. All grades of AVN were considered eligible. Patients were excluded if they had one or more of the following: inability to be followed up regularly, symptoms of oesophagitis or gastritis, age below 18 yr, lactation, and abnormal renal, liver or bone profile. Besides routine physical examination, parameters specifically studied were range of motion, standing and walking time in minutes, pain on visual analogue scale of 0–10 (0, no pain; 10, maximum possible pain) and disability on a scale of 0–10 (0, no disability; 10, totally handicapped).

Baseline investigations included complete blood count, liver, renal and bone profiles, Serum 25 (hydroxy) vit D3 and magnetic resonance imaging (MRI) of both hips. MRI was staged according to the classification of Mitchell et al. [2]. If both hips were affected, for MRI staging the stage of the maximally affected hip was used for analysis. All patients received alendronate 10 mg/day plus a calcium supplement of 1 g/day. Oral vitamin D3 was administered to patients with low vitamin D3 levels. Weight-bearing was not permitted. Patients were evaluated at intervals of 6 weeks and all investigations were repeated at intervals of 3 months. Student's t-test was used to analyse the data. The study was approved by the Hinduja Hospital ethics committee.

In all, 18 patients with AVN of the hip were seen between February and October 2000. Of these, two were excluded (one because of inability to be followed up, one because of an abnormal renal profile). The aetiology of AVN was steroids in 11, alcohol in three and trauma and idiopathic in one case each. Mean age was 34 yr (range 19–44 yr). There were equal numbers of males and females. In 14 patients, both hips were involved. The mean duration of AVN was 13.8 months (range 1–72 months). The mean period of follow-up on alendronate was 24.76 weeks (range 12–36 weeks).

After 12 weeks of treatment, there was a significant improvement in pain, disability, standing and walking capacity (P<0.0003), which was still present at 24 weeks (Table 1Go). Concomitantly, there was significant improvement in the range of movement at the hip (P<0.05). The MRI remained stable in 15 of 16 patients (two at stage C and 14 at stage D before treatment; one at stage C and 15 at stage D after treatment), with resolution of oedema in four and of osteoporosis and joint effusion in one patient each. The analgesic requirement declined considerably in all patients, 13 of 16 needing only an occasional analgesic after 6 weeks.


View this table:
[in this window]
[in a new window]
 
TABLE 1.  Pain, disability, standing and walking time at 6, 12 and 24 weeks

 
The mechanism of the beneficial action of alendronate in AVN is not clear, and one can only speculate. Bisphosphonates inhibit the resorptive action of mature osteoclasts. Furthermore, they increase the level of apoptosis of osteoclasts in vitro and may decrease apoptosis of osteoblasts and osteocytes [3]. These effects may prevent progressive bone resorption and collapse of the bone. Another beneficial effect seen is a decrease in oedema at the site of AVN. Bisphosphonates have been used in many conditions characterized by abnormal bone formation and remodelling; AVN seems to be one more indication. More studies involving larger numbers, early cases and a longer follow-up period are essential if the role of bisphosphonates in AVN is to be evaluated fully.

Notes

Correspondence to: S. Agarwala. Back

References

  1. Mont MA, Carbone JJ, Fairbank AC. Core decompression versus nonoperative management for osteonecrosis of hip. Clin Orthop1996;324:169–78.[Medline]
  2. Mitchell DG, Rao VM, Dalinka MK et al. Femoral head avascular necrosis: correlation of MR imaging, radiographic staging, radionuclide imaging and clinical findings. Radiology1987;167:709–15.
  3. Rodan JD, Fleish HA. Bisphosphonates: mechanisms of action. J Clin Invest1996;97:2692–6.[Free Full Text]
Accepted 22 August 2001