Menopause before age 47 significantly increased the risk of osteoporosis, fragility fractures, and premature mortality over the next 30 years, Swedish investigators reported.

The mortality risk rose by 60%, fracture risk by 70%, and osteoporosis risk almost doubled in women who entered menopause before 47 compared with women who had later onset, as reported online in BJOG.

The explanations for the higher risk of osteoporosis, fracture, and mortality all remained speculative, Ola Svejme, of Lund University, and co-authors wrote.

“The higher fracture risk in women with early menopause in the current study is probably to some extent mediated by a lower bone mineral density (BMD), as the early-menopause cohort had a significantly higher risk of osteoporosis at age 77 and already, at age 48 years, had on average a 0.4 standard deviation (SD) lower BMD than those with late menopause,” the researchers said in their discussion.

“However, the lower BMD level does not seem to be entirely able to explain the increased fracture risk.”

Numerous plausible explanations exist for the higher mortality risk, including an increased comorbidity burden, fracture-related mortality, and differences in diseases, medications, and lifestyle factors, they added.

Several studies have suggested that early menopause predisposes women to osteoporosis and associated fractures. Other studies, however, have found that age at menopause does not influence BMD after age 70, the authors wrote in their introduction.

The Malmö Perimenopausal Study afforded an opportunity to conduct the “ideal study to estimate the long-term impact of menopause on the prevalence of osteoporosis and fracture risk.” Participants in the study were women who were 48 when they enrolled in 1977 and were followed for 29 years for BMD assessment and 34 years for fracture and mortality.

The study initially involved 390 women who were born in Malmö during the last half of 1929. Surviving participants (298) were invited to return for follow-up BMD assessments at 77, and 198 did so. BMD was assessed by single-photon absorptiometry when the women were 48 and at 77.

Osteoporosis was defined as -2.5 SD from the reference value in young adults, resulting in absolute cutoff values of 0.706 g/cm2 for hip BMD and 0.907 g/cm2 for lumbar spine BMD.

Investigators reviewed hospital registries and other databases to identify fractures that occurred in any of the women from enrollment to death, relocation, or Sept. 30, 2011.

The results showed that 61 of the 390 women had early-onset menopause. At enrollment, the two groups did not differ with regard to age at menarche or anthropometrics. Distal forearm BMD was 0.43 SD lower among women who had early menopause.

At age 77, 15 of 27 surviving participants (56%) from the early-menopause group had osteoporosis compared with 52 of 171 (30%) in the late-menopause group (P=0.01). The difference amounted to an osteoporosis risk ratio of 1.83 for the early-menopause group.

Women with early-onset menopause had a fracture rate of 19.45 per 1,000 person-years compared with 11.60 in the late-onset group, resulting in a risk ratio of 1.68 for fragility fracture.

The authors found that 32 of 61 women (52.4%) with early-onset menopause had died by the end of follow-up, compared with 116 of 329 (35.2%) in the late-onset group, which translated into a relative mortality risk of 1.59 among women with early-onset menopause.

Acknowledging limitations of the study, the authors pointed out that only half of the 390 women participated in the follow-up assessment of BMD, making that data less reliable compared with the fracture and mortality data. The study would have been strengthened by use of preplanned spinal x-rays, as many women who have osteoporotic fractures of the spine do not seek medical care at the time of fracture, they added.

Primary source: BJOG
Source reference: Svejme O, et al “Early menopause and risk of osteoporosis, fracture, and mortality: A 34-year prospective observational study in 390 women” BJOG 2012; DOI: 10.1111/j.1471-0528.2012.03324.x.

###

By Charles Bankhead