Serum Sclerostin Levels in Adults With Osteogenesis Imperfecta: Comparison With Normal Individuals and Response to Teriparatide Therapy

Lindsey Nicol, Ying Wang, Rosamund Smith, John Sloan, Sandesh C.S. Nagamani, Jay Shapiro, Brendan Lee, Eric Orwoll

Research output: Contribution to journalArticle


Sclerostin (SOST), a glycoprotein primarily derived from osteocytes, is an important regulator of bone remodeling. Osteogenesis imperfecta (OI) is a heritable disorder of bone characterized by low bone mass, bone fragility, recurrent fractures, and bone deformities. Altered SOST-mediated signaling may have a role in pathogenesis of type I collagen-related OI; however, this has not been evaluated in humans. We measured serum SOST levels in adults with OI who were enrolled in a randomized, placebo-controlled clinical trial that evaluated the effects of osteoanabolic therapy with teriparatide. Compared with age- and sex-matched control participants, mean SOST levels were lower in those with type I or types III/VI OI (p < 0.0001). Receiver operating curve analysis revealed that sclerostin alone or sclerostin plus bone mineral content discriminated patients with OI from controls (area under the curve 0.80 and 0.87, respectively). SOST levels increased in the group of patients with type I OI during therapy with teriparatide (compared with placebo, p = 0.01). The increase was significant at 6, 12, and 24 months of therapy (p ≤ 0.02) and was apparent as early as 3 months (p = 0.06). The magnitude of increases in SOST levels during therapy was inversely correlated with increases in vertebral volumetric bone mineral density (vBMD). Overall, these results suggest that: 1) SOST regulation is fundamentally altered in osteogenesis imperfecta; 2) serum SOST levels could be a biomarker of OI in adults; and 3) alterations in SOST may help predict the response to anabolic therapies in OI.

Original languageEnglish (US)
Pages (from-to)307-315
Number of pages9
JournalJournal of Bone and Mineral Research
Issue number2
Publication statusPublished - Feb 1 2018




ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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