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Anti-sclerostin - is there an indication?
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
2016 (English)In: Injury, ISSN 0020-1383, E-ISSN 1879-0267, Vol. 47, S31-S35 p.Article in journal (Refereed) Published
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Abstract [en]

Several decades ago, a clinical condition that included severe bone overgrowth was described in a few patients in South Africa. The autosomal-recessive disease that later was named sclerosteosis was found to be caused by a mutation in the SOTS gene causing a lack of the protein sclerostin. This protein is produced by osteocytes and exerts its effect as an inhibitor of bone formation by blocking the Wnt signaling pathway. By the use of a monoclonal antibody that can block sclerostin a novel therapeutic pathway for rebuilding bone has been described. Preclinical studies have shown increased bone mass following subcutaneously administered anti-sclerostin antibody in animals with induced postmenopausal osteoporosis as well as in intact male rats and non-human primates. In a phase II study the efficacy and safety of an anti-sclerostin antibody, romosozumab, has been evaluated in 419 postmenopausal women for 12 months. 70, 140 or 210 mg was given subcutaneously monthly or every three months and compared to 70 mg of oral alendronate given once a week or 20 mu g of teriparatide subcutaneously once daily. All dose levels of romosozumab were associated with significant increase in BMD with the most pronounced gain in the group receiving 210 mg where lumbar spine BMD increased with 11.3% from baseline. The BMD for the placebo group decreased by 0.1% while the alendronate group increased 4.1% and the teriparatide increased 7.1%. Biochemical markers revealed a transitory increase in the bone formation marker P1NP while no change in the bone resorption marker beta-CTX. In comparison, teriparatide resulted in an increase for both P1NP and beta-CTX for the complete study period. Even though the rapid gain in BMD is promising when considering a treatment option for osteoporosis and other conditions with bone loss, there are so far no published studies on whether anti-sclerostin can reduce the number of fractures. Wnt signaling might also play an important role in fracture healing with substances that causes an upregulation of the Wnt pathway producing enhancement of the fracture healing process. Healing of experimental fractures in various animal models have shown improvement following subcutaneously administered anti-sclerostin antibody. While there are no published reports on the potential effect of systemically administered anti-sclerostin antibodies on fracture healing in humans.

Place, publisher, year, edition, pages
2016. Vol. 47, S31-S35 p.
Keyword [en]
sclerostin, sclerostin antibody, osteoporosis, fracture healing, anabolic, romosozumab
National Category
Orthopedics
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URN: urn:nbn:se:uu:diva-275567DOI: 10.1016/S0020-1383(16)30008-0ISI: 000367533000008PubMedID: 26768288OAI: oai:DiVA.org:uu-275567DiVA: diva2:900467
Available from: 2016-02-04 Created: 2016-02-04 Last updated: 2017-11-30Bibliographically approved

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Larsson, Sune

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