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Guideline for the management of knee and hip osteoarthritis
We suggest not offering bisphosphonates for people with knee and/or hip osteoarthritis (OA).
Conditional against recommendation
Anti-osteoporotic medications are predominantly used to reduce morbidity and mortality (mainly from fractures) associated with exogenous and endogenous osteoporotic change within bone. Bisphosphonates can inhibit bone resorption and, therefore, are the mainstream medications for osteoporosis. Osteoporosis may be concomitantly present in those with OA.
Evidence from six trials found no statistically significant benefits in symptom relief, and structural and functional improvement. The quality of evidence has varied from moderate to very low, with inconsistent results. A meta-analysis of the two largest knee studies using risedronate 15 mg found the odds ratios (ORs) favouring placebos for Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain (1.73), function (2.03) and stiffness (1.82). However, eight trials (61.5%) reported that bisphosphonates improved pain assessed by Visual Analogue Scale (VAS) scores, and two (38.5%) reported significant improvement in WOMAC pain scores, compared with control groups.There were no statistically significant differences or trends noted for any dose of risedronate. Similarly, there was no difference between the five groups with respect to radiographic joint space narrowing, joint space width or osteophyte formation at 24-month follow-up.105
There is one very low-quality trial conducted in 42 participants with hip OA, demonstrating no effect over 24 months (Appendix 5 of the Guideline for the management of knee and hip osteoarthritis: Technical document).
Biphosphonates currently do not have an indication via the Therapeutic Goods Administration (TGA) for OA, and should be considered as investigational medications only.
Bisphosphonates come with significant side effect profiles and restrictions on some day-to-day activities (eg dental procedures). Treatment with these drugs should be reserved for individuals who meet the Pharmaceutical Benefits Scheme (PBS) guidelines for treatment of their osteoporosis, but not for the management of OA.
We suggest not offering calcitonin for people with knee and/or hip OA
Calcitonin is a natural peptide hormone produced by parafollicular cells (C-cells) in the thyroid gland. The protective activity of calcitonin on bone and cartilage has been demonstrated in many different OA models and preliminary clinical settings.106 Available as an injection or nasal spray since the 1970s to treat osteoporosis, calcitonin inhibits bone resorption by binding and activating to the calcitonin receptor on osteoclasts.
The two phase III studies found no significant effect of salmon calcitonin on total WOMAC, WOMAC subscores and joint space narrowing (Appendix 5 of the Guideline for the management of knee and hip osteoarthritis: Technical document). There is a potentially small effect on markers of bone and cartilage degradation, CTX-I and CTX-II respectively, and no positive balance between bone formation and bone resorption.
There is no randomised controlled trial (RCT) of calcitonin for hip OA; thus, using knee OA data to extrapolate to hip or other OA requires additional caution.
There were markedly higher incidences of gastrointestinal disorders and hot flushes in the active treatment arms of the included studies. No other adverse events were markedly different between the two groups in either study.
We do not recommend offering strontium ranelate for people with knee and/or hip OA.
Strong against recommendation
Strontium ranelate, a bone-acting agent, has the ability to dissociate the bone-remodelling process, and change the balance between bone resorption and formation, which has been suggested to be a potential symptom-modifying effect.
Data from one moderate-quality trial found no effect of strontium ranelate in altering OA symptoms. However, strontium ranelate treatment had a beneficial effect on joint space widening, with a mean difference (MD) of 0.12 mm over three years. Similarly, the risk ratio of radiographic progression (joint space narrowing ≥0.5 mm) favoured strontium ranelate over three years.
As strontium ranelate is not accessible for people in Australia, the working group considered this treatment as unfeasible for use.
Strontium ranelate was well tolerated for the treatment of OA in a study duration over three years. Despite its listed side effects in the approved product information (eg myocardial infarction, venous thromboembolism events, pulmonary embolism, hypersensitivity reaction), the European Medicines Agency recommended in 2014 that strontium ranelate should remain available for individuals with osteoporosis, with restrictions relative to those with existing heart disease. 107 As strontium ranelate would be used as a daily treatment for OA, and its effects could be relatively slow, the potential harm caused by its side effects is a concern.
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Administrative-report.pdf (PDF 2.76 MB)
Algorithm-Holistic-assessment-diagnosis-and-management-of-knee-and-hip-osteoarthritis.pdf (PDF 0.05 MB)
Guideline-for-the-management-of-knee-and-hip-osteoarthritis-2nd-ed-Appendix-1.pdf (PDF 0.04 MB)
Guideline-for-the-management-of-knee-and-hip-osteoarthritis-2nd-ed-Appendix-2.pdf (PDF 0.05 MB)
Implementation-plan.pdf (PDF 1.79 MB)
Public-consultation-summary.pdf (PDF 0.29 MB)
Technical-document.pdf (PDF 5.79 MB)