Teriparatide and denosumab combination therapy and skeletal metabolism

SummarySeveral therapies are available for osteoporis.Understanding the bone turnover changes and their mutualrealtionship gives an overall view and might lead to a targettherapyIntroductionThe aim of this study is to compare the changesin bone turnover markers in patients treated with eitherdenosumab alone, teriparatide (TPTD) alone, or in a thirdtherapeutic scheme, when TPTD was added to patients previ-ously treated with denosumab.MethodsFifty-nine women over 65 years old with severepostmenopausal osteoporosis (evidence of at least twomoderate-severe vertebral fractures) were enrolled in thestudy. Serum samples were collected every 3 months. Theywere assayed for intact N-propeptide of type I collagen(P1NP), C-terminal telopeptide of type I collagen (CTX), in-tact parathyroid hormone (PTH), 25 hydroxy-vitamin D (25OHD), Sclerostin (SOST), and Dickkopf-related protein 1(DKK1). Bone mass density was assessed by dual-energy X-ray absorptiometry at the lumbar spine and at the total hip.ResultsIn the groups treated only with TPTD or withdenosumab, bone turnover markers increased and decreased,respectively. In TPTD group, a later significant increase inDKK1 was observed, while in denosumab group, a progres-sive increase in SOST was associated with a progressive sig-nificant decrease in DKK1.In the group treated first with denosumab and in whichTPTD was added 3 months later, both CTX and P1NPincreased 3 months after the beginning of TPTD. The strongeffect of denosumab on bone turnover seems to be reversed byTPTD treatment.ConclusionsIn this study, we showed that TPTD is able toexpress its biological activity even when bone turnover is fullysuppressed by denosumab treatment. The combination therapy isassociated with significant increases in both DKK1 and SOST.