Prediabetes and fractures in midlife women


In a recent study, midlife women with prediabetes before menopause transition were more likely to experience fractures in postmenopause.

Prediabetes and fractures in midlife women | Image Credit: © tonaquatic - © tonaquatic -

Prediabetes and fractures in midlife women | Image Credit: © tonaquatic - © tonaquatic -

According to a recent study published in JAMA Network Open, prediabetes is associated with increased fracture risk in midlife women.

While fractures, also known as “diabetic bone disease,” have been defined as an end-organ complication of diabetes, there is little data on the association between prediabetes and fractures. However, prediabetes has been associated with reduced trabecular bone microarchitecture and decreased bone turnover.

Disagreements have been seen between clinicians on how severely prediabetes should be treated. Determining an association between prediabetes and bone health would help drive future treatment of prediabetes.

To evaluate the association between prediabetes without type 2 diabetes presence and fractures in midlife women, investigators conducted a cohort study using data from the Study of Women’s Health Across the Nation (SWAN). SWAN was a multicenter cohort study consisting of 3302 premenopausal or early perimenopause women aged 42 to 52 years at baseline.

Data from January 6, 1996, to February 28, 2018, was collected. Patients without an intact uterus and 1 or more ovaries were excluded from the study, along with patients using hormonal therapy or hormonal contraception. On average, patients underwent 1 baseline visit and 16 follow-up visits with a median 1.1 years between visits.

One or more visits before menopause transition (MT) was required for participation in the study. Patients also could not be taking bone-beneficial medication or have type 2 diabetes before MT and needed to have at least 1 visit after MT. 

Bone-beneficial medication includedhormone therapy, calcitriol, calcitonin, denosumab, bisphosphonates, and parathyroid hormone. The start of MT was defined as the first visit in late perimenopause, or as the first menopausal visit in women who transition from premenopause directly to early perimenopause or postmenopause.

The first fracture after the start of MT was defined as the primary outcome of the study. Standardized questionnaires at study visits were used to determine fracture location and occurrence, and fracture adjudication was initiated at the seventh follow-up visit. Following adjudication, 95% of reported fractures were confirmed.

Atraumatic fractures were fractures not linked to a fall from a height under 15.2 cm, motor vehicle accident, playing sports, rapid movement, or an impact from heavy or fast-moving projectiles. Traumatic and atraumatic fractures were included in the analysis, while craniofacial and digital fractures were excluded.

Prediabetes before MT was the primary exposure of the study. The rate of visits from baseline to MT where prediabetes was present was used to determinethe exposure. Prediabetes was defined as a fasting blood glucose level from 100 to 125 mg/dL without taking diabetes medication.

Fasting blood glucose was measured at 2 different SWAN laboratories. A glucose measurement also occurred at the seventh follow-up visit, which was performed with a hexokinase-coupled reaction assay. Covariates measured at the start of MT included age, body mass index, cigarette use, fracture, race and ethnicity, study site, and bone-detrimental medication exposure.

There were 2365 women in the final analysis, aged a mean 49.7 years. Of participants, 25.9% were Black, 11.7% Chinese, 12.7% Japanese, and 49.8% White. Participants experienced an average 3 visits before MT, with 3.3% of women having a fracture before MT and a rate of visits with prediabetes before MT of 0.070.

A mean 12 years occurred between the start of MT and fracture incidence, with 8% of women experiencing a fracture during MT or in postmenopause.A fracture was reported in 11.1% of women with prediabetes and 7.6% of women without prediabetes. 

Prediabetes was reported in 13.3% of patients and was seen more often in Black, Chinese, and Japanese women. The proportion of these patients with prediabetes before MT was 0.524.

Increased fracture risk during MT or postmenopause was found in women with prediabetes before menopause. Investigators recommended further research to determine if treating prediabetes reduces fracture risk.


Shieh A, Greendale GA, Cauley JA, Karvonen-Gutierrez CA, Karlamangla AS. Prediabetes and fracture risk among midlife women in the study of women’s health across the nation. JAMA Netw Open. 2023;6(5):e2314835. doi:10.1001/jamanetworkopen.2023.14835

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