Genetic disorder sheds light on enzyme’s role in bone metabolism


Washington : Pycnodysostosis is a genetic disease characterised by short stature, which opens a window into how joints are destroyed by arthritis.

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The condition is caused by deficiency of an enzyme known as cathepsin K which hampers osteoclasts (cells that break down bone in bone modelling and repair), leading to bone resorption, dense, brittle bones.

Cathepsin K’s role in bone metabolism has largely been studied using mouse models, but a new study examines its role in bone resorption in a human patient and shows that it is not required to break down bone.

Bone resorption is the wearing away of bone tissue, which can eventually lead to osteoporosis, spinal deformities and fractures.

Led by Yrjö T. Konttinen of Helsinki University Central Hospital, Finland, the study involved a 55-year-old female patient with pycnodysostosis who also developed psoriatic arthritis, (associated with psoriasis, a skin and nail disease).

Since the patient lacked cathepsin K due to her condition, researchers hypothesised that this would protect her from the bone erosions in the hands and feet normally seen in psoriatic arthritis, according to a Helsinki University release.

However, she did in fact develop extensive erosions and destructive bone changes in her hands. Blood analysis was conducted to examine the proteinases (enzymes that break down proteins) responsible for bone degradation as well as the cellular mechanisms of bone resorption.

The analyses showed that the osteoclasts formed by the patient lacked cathepsin K, which was expected. Surprisingly, however, this deficiency did not prevent cells from resorbing bone, although the resorption was abnormal.

The study was published in the November issue of Arthritis & Rheumatism.