How we can monitor denosumab treatment effects in osteoporosis?

Osteoporosis is one of the most frequent skeletal diseases, mainly affecting post-menopausal women, and characterised by enhanced bone resorption by the bone cells osteoclasts, decrease of bone mineral density (BMD), and impairment of bone microarchitecture. A very effective clinical treatment for osteoporosis is denosumab, an antibody that blocks the RANKL protein, the molecule responsible for osteoclast formation and activation. At the time of denosumab initiation, patients with osteoporosis can be either treatment-naïve or pre-treated with drugs that reduce bone resorption, such as the bisphosphonate zoledronic acid (ZOL), or enhance bone formation, such as teriparatide (TPTD). How can skeletal effects be monitored during and after treatment with denosumab? Next to the evaluation of BMD changes, other molecules related to bone remodeling can be measured, the so called Bone Turnover Markers (BTMs), such as P1NP, a marker of bone formation, or CTX, a marker of bone resorption. The exact role of BTMs as monitoring tools for anti-osteoporosis therapies needs further clarification. To this effect, a recent study that involved three ECTS Academy Members has been published in Bone. In this work, Elena Tsourdi, Martina Rauner, Athanasios Anastasilakis and colleagues, demonstrated that in a group of 82 post-menopausal women with low bone mass, lumbar spine BMD increased after 12 months of denosumab treatment irrespectively of previous treatments with ZOL or TPTD, and even in women who were therapy-naïve before receiving denosumab. Moreover, P1NP and CTX decreased significantly with denosumab reaching the same lowest levels in pre-treated and treatment-naïve women. More interestingly, they found that concentrations of a molecule called myostatin (involved in muscle, fat and bone metabolism) were lower in women pre-treated with TPTD as compared to the other two groups. All these findings, that need further validation in larger patient cohorts, are important for a better management of people affected by osteoporosis and for monitoring the positive effects of anti-osteoporosis treatments.

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