Serum sclerostin and sympathetic skin response: relationship with myeloma bone disease

Abstract

Abstract Background Myeloma bone disease (MBD) is a common complication that significantly contributes to morbidity and mortality in multiple myeloma (MM). Serum sclerostin level and sympathetic activity can affect MBD. The purpose of this study is evaluation of serum sclerostin level and sympathetic activity (using sympathetic skin response “SSR”) in MM patients, and studying the relationship between both of them as well as their relationship with MBD. 35 smoldering myeloma patients (group I) and 35 newly diagnosed MM (group II) and 35 controls (group III) were included in the study. All the participants were subjected to complete history taking, and clinical examination. Assessment of serum sclerostin level, SSR, MM stages [by the international staging system (ISS)], MBD grading (according to the Durie–Salmon staging system) were done for all patients within 7 days from the diagnosis. Results Undetectable and decreased SSR amplitude are significantly more detected in group I and II (compared with group III). Autonomic manifestations, and loss of SSR is significantly more detected in group II than group I. Autonomic manifestations were absent in group III. SSR amplitude of median and tibial nerves is significantly decreased in group II than group I and III. MBD was detected in all patients of group II. Serum sclerostin and LDH were significantly increased in group II than group I. Group I and II had significantly higher levels of sclerostin when compared with group III. Group II had significantly higher levels of sclerostin and lower levels of ALP in comparison with group I. Serum sclerostin level was correlated positively with LDH and negatively with ALP and SSR amplitude. MBD was significantly affected by ISS stage III, LDH level, SSR affection and serum sclerostin level ≥ 0.40 ng/ml. SSR response affection was the most significant risk factor for advanced MBD followed by increased sclerostin level. Conclusions Serum sclerostin level was significantly increased and sympathetic activity was significantly decreased in MBD. Loss of the SSR response was the most significant risk factor for advanced MBD followed by increased sclerostin level. Recommendations Potentially validating the use of bone-turnover markers in larger studies, in addition to electrophysiological examination of SSR to stratify patients who are at high-risk for progressive MBD, as the use of newer agents with anabolic effects such as anti-sclerostin antibodies have shown potential in repair of MBD. These newer agents could potentially change the treatment landscape in patients with MBD.

Keywords

• Sympathetic skin response
• Multiple myeloma
• Smoldering myeloma
• Circulating sclerostin
• Myeloma bone disease