Bone trumping cartilage as the key to knee OA

Deficits in bone are emerging as the central underlying feature of knee osteoarthritis, raising the hope that treatments targeting bone might significantly modify the disease process, a recent review by Australian rheumatologists has concluded.

Professor Flavia Cicuttini, head of rheumatology at the Alfred Hospital in Melbourne, and colleagues described how ‘Wolff’s law’ provides a rationale for what we know about the disease.

Writing in Arthritis Research and Therapy, they said the law, formulated by German anatomist and surgeon Julius Wolff more than a century ago, theorises that bone adapts to repeated loading.

They suggest that an acute event like a cruciate ligament rupture leads to loss of periarticular bone, microfractures and sequent healing, followed by subchondral sclerosis, impaired nutrient supply to cartilage, cartilage degeneration and early OA.

Similar process are likely to occur in response to chronic trauma, for example from overloading associated with obesity, and possibly in primary OA where there is no obvious precipitant.

“These concepts help explain findings over recent years, particularly from MRI studies, that some of the earliest changes in knee OA are occurring in the bone,” Professor Cicuttini told the limbic.

“Bone is a dynamic structure which responds to loading, and there are very early changes in knee OA which we now know is a disease of the whole joint.

“Bone is important in providing nutritional and structural support to overlying cartilage and it responds to biomechanical loading by expanding and/or thickening.

“This may have an impact on the underlying cartilage as the intimate relationship between cartilage and bone is essential to the health of the knee joint.”

The most promising disease-modifying osteoarthritis drugs (DMOADs) all target bone rather than cartilage.

“For example, strontium ranelate is effective in improving symptoms and slowing structural progression of knee OA,” Professor Cicuttini says.

“Although the cardiovascular effects of strontium will limit its use, this has provided a proof of concept that targeting bone may be one approach to disease modification.”

More evidence from randomised clinical trials is needed before DMOADs can be used, but results of current trials should emerge in the next 2-3 years.

“DMOADS are likely to have a very significant impact,” she says.

“End-stage knee OA is treated with joint replacements and an effective  DMOAD would slow progression.

“In some people it would mean that their OA never progresses to the point where they would need a joint replacement.

Professor Cicuttini says results for primary joint replacement surgery are generally very good but the results for revision surgery are much poorer, with the life span of each revision decreasing by about 50%.

“Some patients may be able to delay joint replacement by using DMOADs, for example from age 55 to age 65, so the likelihood of needing a revision would be significantly reduced.

“Delaying the need for joint replacement, while maintaining good functioning and quality of life, is likely to have major impact on the cost of OA and also improve patient outcomes,” she says.



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