Effects of Metformin on Bone Turnover in Polycystic Ovary Syndrome

Bone tissue. Coloured scanning electron micrograph (SEM) of cancellous (spongy) bone. This tissue, found in the interior of bones, is characterised by a honeycomb arrangement of trabeculae (columns) and spaces. This honeycomb structure provides support and strength to the bone. Magnification: x 15 when printed 10 centimetres wide.
In a cohort of premenopausal women with PCOS, metformin treatment for 3 months was associated with reduced bone turnover.

Metformin treatment is associated with reduced bone turnover in premenopausal women with polycystic ovary syndrome (PCOS), according to study results published in Fertility and Sterility.

Limited data are available regarding metformin’s effects on bone metabolism and turnover in PCOS. Researchers conducted this post hoc analysis of a prospective multicenter trial to assess the effects of metformin on bone formation and resorption in women with PCOS. In the original study, 74 non-obese and 44 obese women with PCOS (average age, 27.6 years) were randomly assigned to receive 3 months of metformin (n=57) or placebo (n=61). Non-obese women assigned to metformin received 500 mg and 1000 mg daily and obese women received metformin 1000 mg twice daily.

Patients’ serum levels of markers procollagen type 1 amino-terminal propeptide (P1NP) and carboxy-terminal cross-linking telopeptide of type 1 collagen (CTX) were measured at baseline and after treatment. Between-group baseline serum levels were similar in the metformin and placebo groups, as were clinical, hormonal, and metabolic parameters across the study cohort. Compared with non-obese women, obese women had lower average baseline levels of P1NP (50.0 vs 39.6 µg/L, respectively; P =.003) and CTX (0.46 vs 0.32 µg/L, respectively; P <.001).

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After 3 months of treatment, obese and non-obese women in the metformin group experienced significant reductions in both markers. Non-obese women saw an average P1NP decrease of 25.7% (P <.001) and CTX decrease of 31.1% (P <.001) and obese women saw an average P1NP decrease of 32% (P <.001) and CTX decrease of 24.1% (P =.022). This decrease was not affected by androgen status. Conversely, both obese and non-obese women in the placebo group experienced no significant reductions in either marker level.

Several study limitations were noted, including its short duration and criteria for subject selection.

In summarizing their findings, the researchers said, “metformin treatment of premenopausal women with PCOS for 3 months was associated with reduced bone turnover…However, long-term intervention studies with [bone mineral density] measurements and fracture assessment are necessary to demonstrate the effects of metformin on bone turnover and remodeling in PCOS conclusively.”

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Lingaiah S, Morin-Papunen L, Risteli J, et al. Metformin decreases bone turnover markers in polycystic ovary syndrome: a post hoc study [published online June 18, 2019]. Fertil Steril. doi:10.1016/j.fertnstert.2019.04.013