Osteonecrosis of the Hip and Bisphosphonate Treatment

• Status: Unknown status
• Trial end date: 2013-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Osteonecrosis of the hip is an important cause of musculoskeletal disability and finding therapeutic solutions has proven to be challenging. Osteonecrosis means death of bone which can occur from the loss of the blood supply or some other means. Although any age group may develop osteonecrosis, most patients are between 20 and 50 years old. The most common risk factor is a history of high steroid treatment for some medical condition. The next most common associated condition is a history of high alcohol use. There are some cases of osteonecrosis that occur in patients that are otherwise completely healthy with no detectable risk factors.

In the earliest stage of the disease, x-rays appear normal and the diagnosis is made using MRI. The advanced stages of osteonecrosis begin when the dead bone starts to fail mechanically through a process of microfractures of the bone. As the disease progresses, the surface begins to collapse until, finally the integrity of the joint is destroyed. A wide range of surgical treatments with variable success rates have been proposed for the treatment of the osteonecrosis to preserve joint integrity, including core decompression, whereby the venous hypertension that ensues is lessened and revascularisation may be induced leading to bone repair. Nonsurgical treatment options are limited and usually result in a poor prognosis. Early stage disease can be treated with protected weight bearing and physiotherapy, however some studies have shown protected weight bearing to be associated with a greater than 85% rate of femoral head collapse. Unfortunately most studies indicate that the risk for disease progression is greater with nonsurgical treatment than with surgical intervention. There are no established pharmaceuticals for the prevention of treatment of osteonecrosis. Evidence is increasing that the nitrogen containing bisphosphonates may be beneficial in the treatment of osteonecrosis. One bisphosphonates (alendronate) has been evaluated in 60 patients diagnosed with osteonecrosis of the hip. Recent clinical studies have shown very promising results. All patients had symptomatic improvement after one year. Although the follow up time ranged from 3 months to 5 years, only 6 patients progressed to the point of needing surgery.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Sydney
• Collaborator: Novartis
• Treatments: Diphosphonates; Zoledronic Acid

Criteria

Inclusion Criteria:

1. aged between 18-90 years,

2. symptoms of pain and disability in at least one hip joint, or

3. positive MRI findings stage I or II on the ARCO classification

Exclusion Criteria:

1. previous hip joint surgery on the affected hip

2. severe pain and disability at rest if treating clinician has recommended surgery

3. radiographic or MRI findings suggestive for stage III and IV on the ARCO classification

4. any iv bisphosphonate within the prior 2 years or any prior use of bisphosphonate preparations, except according to the washout schedule:

• 2 years (if use > 48 weeks),

• 1 year (if used > 8 weeks but < 48 weeks)

• 6 months (if used > 2 weeks but < 8 weeks)

• 2 months (if used < 2 weeks)

5. active primary hyperparathyroidism

6. hypothyroidism, not appropriately controlled with long-term thyroxine therapy

7. history of iritis or uveitis, except due to trauma, and resolved for > 2 years prior to study

8. self-reported history of diabetic nephropathy or retinopathy (if diabetic, Hb A1c > 10%)

9. urine dipstick greater than or equal to 2+ protein at screening

10. AST or ALT greater than twice the upper limit of normal and/or alkaline phosphatase greater than twice the upper limit of normal

11. serum calcium > 2.75 mmol/L (11.0 mg/dL) or < 2.00 mmol/L (8.0 mg/dL)

12. serum 25-hydroxyvitamin D concentrations < 15 ng/L m) baseline renal insufficiency (calculated creatinine clearance less than 40 mL/min and serum creatinine greater than 175 mol/L) at V1

13. a history of invasive malignancy of any organ system, treated or untreated, in the past five years; excluding, basal cell or squamous cell carcinoma of the skin, colonic polyps with non-invasive malignancy which have been removed, ductal carcinoma in-situ (DCIS), and carcinoma in-situ (CIS) of the uterine cervix

14. any candidate patient with severe dental problems or current dental infections and/or any candidate patient with recent or impending dental surgery within three months of dosing

15. women of childbearing potential not using the contraception method(s) specified in this study (specify), as well as women who are breastfeeding