Bone effects of metformin monotherapy and its combination with teneligliptin: A 12-week follow-up study in patients with type 2 diabetes mellitus.

AIMS: The skeletal effects of metformin monotherapy and in combination with teneligliptin are not well illustrated in patients with T2DM. To address this, we conducted an observational study to evaluate the effect of these oral hypoglycemic agents on bone turnover markers. METHODS: We recruited patients with T2DM and first-ever prescribed metformin monotherapy or metformin combined with teneligliptin from a tertiary care teaching hospital in New Delhi, North India. Both bone formation and resorption markers, IL-6 and PTD, were estimated along with glycated hemoglobin at baseline and 12 weeks. RESULTS: In both groups, hbA1c levels decreased significantly from baseline to 12 weeks. In the metformin-treated group, ß-CTX, sRANKL, IL-6, and PTD decreased significantly, and no significant changes were observed in P1NP, OC, BAP, or OPG at 12 weeks from baseline. In the metformin + teneligliptin group, BAP, ß-CTX, sRANKL, IL-6, and PTD decreased significantly, and no significant changes were observed in P1NP, OC, or OPG after 12 weeks from baseline. CONCLUSIONS: The positive bone outcome of metformin or teneligliptin was linked to bone resorption rather than bone formation and was independent of changes in HbA1c or PTD. However, these results must be confirmed with well-designed RCTs with more extended follow-up periods.

The impact of antiseizure medication on bone heath: A systematic review of animal studies.

BACKGROUND: Antiseizure medications (ASMs) are known to potentially impact bone health, but existing literature presents conflicting results regarding their specific effects on bone mineralization, metabolism, and quality. OBJECTIVE: This systematic review aims to establish a consensus regarding the influence of ASMs on bone health based on existing preclinical studies. METHODS: Following SYRCLE and PRISMA guidelines, we conducted a systematic search in PubMed, Science Direct, and Google Scholar to identify relevant studies. Ultimately, 21 articles were selected for inclusion in this review. RESULTS: Among the chosen studies, approximately half involved Wistar rats as experimental subjects. Levetiracetam and sodium valproate were the most frequently investigated drugs, with a typical treatment duration of 10-12 weeks. These studies exhibited a low risk of bias in aspects like sequence generation, random housing, random outcome assessment, and reporting bias. However, blinding in performance, allocation concealment, and detection were often rated as having a high risk of bias. The collective findings suggest that prolonged ASM use leads to reduced bone mineral density, altered bone turnover marker levels (including hypovitaminosis D, hypocalcemia, and secondary hyperparathyroidism), deterioration of bone microarchitecture, and decreased mechanical strength. CONCLUSION: The adverse effects on bone associated with ASMs are not limited to enzyme-inducing drugs, as newer generation ASMs may also contribute to these effects. Hypovitaminosis D alone may not be solely responsible for ASM-induced bone issues, suggesting the involvement of other mechanisms. Furthermore, substantial variations were observed in the results of different preclinical studies on individual ASMs, highlighting the need to standardize animal study methodologies to enhance reproducibility and reduce variation.

Metformin: Is It the Well Wisher of Bone Beyond Glycemic Control in Diabetes Mellitus?

Both diabetes mellitus and osteoporosis constitute a notable burden in terms of quality of life and healthcare costs. Diabetes mellitus affecting the skeletal system has been gaining attention in recent years and is now getting recognized as yet another complication of the disease, known as diabetic bone disease. As this condition with weaker bone strength increases fracture risk and reduces the quality of life, so much attention is being paid to investigate the molecular pathways through which both diabetes and its therapy are affecting bone metabolism. Out of many therapeutic agents currently available for managing diabetes mellitus, metformin is one of the most widely accepted first choices worldwide. The purpose of this review is to describe the effects of biguanide-metformin on bone metabolism in type 2 diabetes mellitus including its plausible mechanisms of action on the skeleton. In vitro studies suggest that metformin directly stimulates osteoblasts differentiation and may inhibit osteoclastogenesis by increasing osteoprotegerin expression, both through activation of the AMPK signaling pathway. Several studies in both preclinical and clinical settings report the favorable effects of metformin on bone microarchitecture, bone mineral density, bone turnover markers, and fracture risk. However, animal studies were not specific in terms of the diabetic models used and clinical studies were associated with several confounders. The review highlights some of these limitations and provide future recommendations for research in this area which is necessary to better understand the role of metformin on skeletal outcomes in diabetes.

Alliance between selective serotonin reuptake inhibitors and fracture risk: an updated systematic review and meta-analysis.

PURPOSE: In the past few years, several fracture-related events have been reported with chronic use of selective serotonin reuptake inhibitors (SSRIs) throughout the globe. Hence, an updated systematic review and meta-analysis was necessary to ascertain the risk involved. The present work evaluated the association of SSRIs with the risk of fracture in adults. METHODS: We systematically searched PubMed, Cochrane library, and Google Scholar for observational studies on the same from inception to April 2019. Screening, data extraction, and risk of bias assessment were conducted independently by 2 authors. RESULTS: We assessed 69 studies out of which 37 (14 case-control, 23 cohorts) were included. Our results showed that SSRIs were significantly associated with an increased fracture risk (relative risk of 1.62, 95% CI 1.52-1.73; P < 0.000; I2 = 90.8%). The relative risk values for case-control and cohort studies were found to be 1.80 (95% CI 1.58-2.03; P < 0.000; I2 = 93.2%) and 1.51 (95% CI 1.39-1.64; P < 0.000; I2 = 88.0%) respectively. Subgroup analysis showed that association of risk of fracture persisted regardless of geographical location, study design, risk factors, defined daily dose, SSRI use duration, site of the fracture, period of study and after adjusting for depression, physical activity, gender, and age group. The sensitivity analysis data shows that the studies adjusted for bone mineral density and osteoporosis show lesser fracture risk. CONCLUSION: Our findings suggests that SSRIs may be associated with an increased fracture risk; hence, bone health should be taken into consideration while prescribing this class of drugs.