Teriparatide and denosumab combination therapy and skeletal metabolism.

Several therapies are available for osteoporis. Understanding the bone turnover changes and their mutual realtionship gives an overall view and might lead to a target therapy INTRODUCTION: The aim of this study is to compare the changes in bone turnover markers in patients treated with either denosumab alone, teriparatide (TPTD) alone, or in a third therapeutic scheme, when TPTD was added to patients previously treated with denosumab. METHODS: Fifty-nine women over 65 years old with severe postmenopausal osteoporosis (evidence of at least two moderate-severe vertebral fractures) were enrolled in the study. Serum samples were collected every 3 months. They were assayed for intact N-propeptide of type I collagen (P1NP), C-terminal telopeptide of type I collagen (CTX), intact parathyroid hormone (PTH), 25 hydroxy-vitamin D (25 OHD), 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. RESULTS: In the groups treated only with TPTD or with denosumab, bone turnover markers increased and decreased, respectively. In TPTD group, a later significant increase in DKK1 was observed, while in denosumab group, a progressive increase in SOST was associated with a progressive significant decrease in DKK1. In the group treated first with denosumab and in which TPTD was added 3 months later, both CTX and P1NP increased 3 months after the beginning of TPTD. The strong effect of denosumab on bone turnover seems to be reversed by TPTD treatment. CONCLUSIONS: In this study, we showed that TPTD is able to express its biological activity even when bone turnover is fully suppressed by denosumab treatment. The combination therapy is associated with significant increases in both DKK1 and SOST.

Prevalence, pathogenesis, and treatment options for mastocytosis-related osteoporosis.

Mastocytosis is a rare condition characterized by abnormal mast cell proliferation and a broad spectrum of manifestations, including various organs and tissues. Osteoporosis is one of the most frequent manifestations of systemic mastocytosis, particularly in adults. Osteoporosis secondary to systemic mastocytosis is a cause of unexplained low bone mineral density that should be investigated when accompanied by suspicious clinical elements. Bone involvement is often complicated by a high recurrence of fragility fractures, mainly vertebral, leading to severe disability. The mechanism of bone loss is the result of different pathways, not yet fully discovered. The main actor is the osteoclast with a relative or absolute predominance of bone resorption. Among the stimuli that drive osteoclast activity, the most important one seems to be the RANK-RANKL signaling, but also histamine and other cytokines play a significant role in the process. The central role of osteoclasts made bisphosphonates, as anti-resorptive drugs, the most rational treatment for bone involvement in systemic mastocytosis. There are a few small studies supporting this approach, with large heterogeneity of drug and administration scheme. Currently, zoledronate has the best evidence in terms of gain in bone mineral density and bone turnover suppression, two surrogate markers of anti-fracture efficacy.