Bone Status in Obese, Non-diabetic, Antipsychotic-Treated Patients, and Effects of the Glucagon-Like Peptide-1 Receptor Agonist Exenatide on Bone Turnover Markers and Bone Mineral Density

Abstract

Background: Low bone mineral density (BMD) may constitute an underestimated comorbidity in schizophrenia patients undergoing long-term antipsychotic treatment. Glucagon-like peptide 1 (GLP-1) receptor agonists are antidiabetic drugs, which may also affect bone turnover.Methods: In planned secondary analyses of a 3 months, double-blind, randomized, placebo-controlled trial (n = 45), we explored effects of the GLP-1 receptor agonist exenatide 2 mg once-weekly (n = 23), or placebo (n = 22) on bone turnover markers (BTMs) and BMD in chronic, obese, antipsychotic-treated patients with schizophrenia spectrum disorder. Baseline BTMs were compared to sex- and age-adjusted reference values from a Danish population cohort, and T- and Z-scores were calculated for BMD.Results: In women (n = 24), all baseline BTM measurements of procollagen type I N-terminal propeptide (PINP) and C-terminal cross-linking telopeptide of type I collagen (CTX) were within reference values. In men (n = 21), 5% displayed lower PINP and 14% displayed lower CTX. One patient displayed BMD Z-score < −2, and 23% of patients (17% of women and 29% of men) displayed −2.5 < T-scores < –1 indicating osteopenia, but none had osteoporosis. After treatment, PINP decreased at trend level significance (P = 0.05), and body mass index BMD increased for L2–L4 (P = 0.016). No changes in bone markers were significant after correction for mean prolactin levels.Conclusions: Sex- and age-adjusted measures of bone status in chronic, obese, antipsychotic-treated patients appeared comparable to the reference population. Subtle changes in bone markers during 3 months exenatide treatment may suggest beneficial effects of GLP-1 receptor agonists on bone status in antipsychotic-treated patients, and further studies should consider the potential influence of prolactin.

Glucagon-like peptide 1 (GLP-1)

“…In non-diabetic, overweight men, GLP-1 infusion seems to reduce the extent of bone resorption in a similar way to GIP [787]. However, in obese, non-diabetic patients under anti-psychotic drugs, exenatide failed to modify significantly the pattern of bone remodeling [870]. In contrast, liraglutide was capable of enhancing bone formation in obese weight-reducing women while having no effects on bone resorption [871].…”

Association between bile acid metabolism and bone mineral density in postmenopausal women

“…However, to date, only few clinical studies have shown the association between bile acid metabolism and BMD. Moreover, the underlying mechanisms remain unknown (9,10).…”

Effects of Incretin Therapy on Skeletal Health in Type 2 Diabetes—A Systematic Review

“…( 42 ) Furthermore, in a trial involving obese people without diabetes who were on antipsychotic treatment, a 3‐month exposure to exenatide did not lead to any changes in BMD in the lumbar spine, femoral neck, or total hip. ( 43 )…”

“…However, no changes were observed in these measurements in the liraglutide treatment group. (40) Overall, the studies suggest that GLP-1 RAs, particularly liraglutide (39,40,44,45) and exenatide, (41)(42)(43)46,47) may have varying effects on bone metabolism and BMD in different populations, including T2D people and obese people, although the effect of the drugs is generally neutral. The impact on bone health appears to be influenced by factors such as weight loss, genetic mutations, and the presence of diabetes.…”