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.

Patients with ankylosing spondylitis (AS) have an increased risk of bone loss and vertebral fractures. In this study, we explored the hypothesis that the excess bone loss and vertebral fractures might be related with the activity of the Wingless signaling pathway, and in particular with the serum levels of its circulating inhibitors, Sclerostin and Dickkopf-1 (DKK1). We recruited 71 patients diagnosed with AS. Lateral radiographs of the total spine were analyzed to detect the presence of vertebral fractures, and bone mineral density (BMD) was assessed in all patients using dual X-ray absorptiometry at lumbar spine and proximal femoral site. Blood samples were obtained and levels of C-reactive protein (CRP), DKK1, and Sclerostin were measured. Blood samples from 71 healthy sex- and age-matched volunteers were collected to be used as controls. Vertebral fractures were detected more commonly among men than in women (29 vs 8 %, respectively). DKK1, but not Sclerostin serum levels, were inversely correlated to lumbar spine Z-score BMD. Patients with one or more prevalent vertebral fractures had significantly higher DKK1 levels, without significant difference in Sclerostin serum levels. A significant positive correlation was found between DKK1 serum levels and CRP (r = 0.240, p = 0.043). The association we found between serum DKK1 levels and BMD values and vertebral fracture prevalence suggests that DKK1 might contribute to the severity of osteoporosis in AS.

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.

Pivotal studies on ibandronic acid efficacy in terms of antifracture effects on nonvertebral fractures had some intrinsic limitations. However, a large body of indirect evidence suggests that ibandronate has significantly sustained vertebral and nonvertebral antifracture efficacies in women with postmenopausal osteoporosis, in comparison to those observed with other nitrogen-containing bisphosphonates. Discrepancies in efficacy between the available bisphosphonate regimens appear to be a function of dose rather than to inherent differences in their respective therapeutic potential. Drugs or treatment regimens that minimize the risk of osteoporotic fractures and make the treatment of osteoporosis more convenient and suitable for patients are preferred: ibandronic acid marketed at oral doses of 150 mg once monthly and 3 mg quarterly as intravenous injection has these characteristics. The safety profile of ibandronic acid treatment appears to be good overall and in some cases better than that of other nitrogen-containing bisphosphonates.

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