A new bone balance index was developed by researchers utilizing bone turnover markers to measure net bone formation to more accurately predict when women might experience increased rates of bone loss during the menopausal transition. This new index considers both bone formation and breakdown in determining overall bone balance, according to data published in the Journal of Clinical Endocrinology & Metabolism.

The frequency of osteoporosis increases with age. Structurally weak bones that are more susceptible to fractures characterize osteoporosis. Aging is a major risk factor, and women are particularly susceptible to bone loss during the menopausal transition. To better predict bone loss during this time, Albert Shieh, MD, a fellow at the University of California, Los Angeles, and colleagues created the bone balance index using data from a group of 685 women.

“At present, we can measure markers of bone breakdown (resorption) and formation. However, we hypothesized that to better predict the amount of bone mass that will be lost in the future, these markers should be combined in an ‘index’ to reflect both processes, rather than being interpreted in isolation,” said Dr Shieh told Endocrinology Advisor.

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“Indeed, we found that the ability of our new bone balance index predicted future bone loss across the menopause transition better than the bone resorption marker alone.”

The participants were between 42 and 52 years of age and were premenopausal or in early perimenopause upon enrollment. In contrast to previous studies that included or were restricted to postmenopausal women, this study exclusively assessed premenopausal and early perimenopausal women. Participants experienced final menstruations during follow-up. The researchers measured bone mineral density (BMD) every year during the study.

The bone balance index was created by estimating the relationship between markers of bone resorption and bone formation when total resorption equals total formation with stable BMD in the 685 women, more than 5 years prior to the final menstrual period.

The researchers found that the bone balance index was a stronger predictor of bone loss than the measurement of bone breakdown alone.

Results showed that the bone balance index was greater — more favorable — in women with greater BMIs (=.03) and lower — less favorable — in those closer to the final menstrual period (=.007) after adjustment for covariates, with each standard deviation (SD) decrement in the index being linked to a 0.27%-per-year faster decline in BMD at the lumbar spine (=.04). Data also indicated that with each SD decrement, there was a 28% higher odds of faster-than-average loss of BMD at the lumbar spine (=.008; c-statistic, 0.76).

The researchers noted, however, that the bone balance index was not associated with decline in BMD at the femoral neck and that urinary N-telopeptide alone was not associated with BMD decline at either the lumbar spine or femoral neck.

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“This novel approach to assessing an individual’s bone health may help identify which women are at risk of losing vertebral BMD across the menopause transition,” Dr Shieh explained.

“More studies are needed to test whether this index is useful for predicting bone loss after the menopause transition, and if it is useful for predicting fractures.” The bone balance index explained approximately 20% of the variance in the decline in BMD.

“There is not necessarily a threshold proportion of variance explained that validates a marker, but 20% for a biochemical marker is pretty good,” said Dr Shieh. The ability of the bone balance index to predict BMD specifically in the lumbar spine could be due to the menopausal transition.

“Bone loss was more pronounced at the lumbar spine among the women that were included in this study because they were younger and moving across the menopause transition, when trabecular bone loss predominates,” Dr Shieh noted.

“We expect that if the study participants had been older, when cortical bone loss predominates, and bone loss was more pronounced at sites such as the hip, the index would have been better at predicting bone loss at that site instead.”

Summary and Clinical Applicability

This new novel bone balance index appears to be able to predict long-term changes in vertebral BMD in postmenopausal women.


  1. Shieh A, Han W, Ishii S, Greendale GA, Crandall CJ, Karlamangia AS. Quantifying the Balance Between Total Bone Formation and Total Bone Resorption: An Index of Net Bone Formation. 2016. J Clin Endocrinol Metab. doi:10.1210/jc.2015-4262.

This article originally appeared on Endocrinology Advisor