Trabecular Bone Score and Bone Remodelling Markers Identify Perimenopausal Women at High Risk of Bone Loss

Gala Gutierrez-Buey; Patricia Restituto; Sonsoles Botella; Ignacio Monreal; Inmaculada Colina; Macarena Rodríguez-Fraile; Amparo Calleja; Nerea Varo


Clin Endocrinol. 2019;91(3):391-399. 

In This Article

Abstract and Introduction


Context: Bone loss is accelerated in the late perimenopause and early menopause. The date of the final menstrual period cannot be stated until 1 year after it has ended, and at that time, most of the rapid bone loss phase will have elapsed. Therefore, early detection of bone loss is crucial.

Objectives: To evaluate the utility of bone turnover markers (BTM) to identify the women who are more likely to lose more bone mass during the transition to menopause and quantify the loss of bone quality measured by trabecular bone score (TBS).

Design, patients and setting: Sixty-four healthy premenopausal women, mean age between 44 and 57 years old, were enrolled and followed up for 5 years. Clinical features, lifestyle, bone densitometry, TBS and BTM (CTX, P1NP and osteocalcin) were measured at baseline and follow-up.

Results: All women had densitometrically normal bone at the time of enrolment. After 5 years, 48.4% had normal bone mineral density, 45.8% low bone mass and 6.3% osteoporosis. Women with osteopenia/osteoporosis at follow-up had higher CTX and P1NP at enrolment compared with women with densitometrically normal bone. The areas under the curve for the prediction of low bone mass or osteoporosis were 0.69 (P = 0.011) for P1NP, 0.69 for CTX (P = 0.013) and 0.77 (P 0.001) for OC. A significant correlation was found between P1NP increase after 5 years and the decrease in lumbar bone density (r = −0.383, P = 0.002). At baseline, 7 (10.9%) women had deteriorated microarchitecture (TBS < 1.3). Three of these women developed osteoporosis and four osteopenia at follow-up.

Conclusions: Women with higher P1NP and CTX and lower TBS at baseline had lower BMD in the transition to menopause suggesting these novel tools could have potential use in identifying women at high risk of rapidly decreasing bone mass.


The hormonal changes that occur throughout transmenopause have a profound impact on female skeletal health and bone strength. Oestrogen deficiency stimulates RANKL production prolonging the life span of osteoclasts and reducing the life span of osteoblasts, aggravating the negative bone balance in the bone multicellular unit. Bone turnover rate accelerates during 3-5 years before the last menstrual period and slows down again 3-5 years after the last menstrual period.[1] All these changes lead to accelerate bone loss substantially in the late perimenopause and it continues at a similar pace in the first postmenopausal years. The mean rate of bone loss during this 5-year period is about 10%, while age-related bone loss in the sixth decade is 0.5% per year.[2]

Bone mass declines are accompanied by deleterious changes in trabecular and cortical microarchitecture. Thirteen per cent of trabecular bone loss in postmenopausal women can be attributed to the decrease in trabecular numbers and the increase in trabecular perforation.[3] It is important to note that trabecular perforation is considered an irreversible microarchitectural change, so that bone loss, strength and microarchitecture that occurs during transmenopause are permanent.[4]

More knowledge is needed about the factors that may identify women who are at high risk for bone loss or fracture as they enter menopause and therefore are more likely to require future management.

Dual-energy X-ray absorptiometry (DXA) is the standard method of measuring bone mass; however, it provides information of bone mass only and has some limitations.[5,6] The trabecular bone score (TBS) is a novel tool for evaluating bone microarchitecture. This textural index indirectly assesses bone trabecular microarchitecture using lumbar spine images obtained by DXA. The TBS derived from DXA images correlates with the 3-dimensional microarchitecture parameters measured by quantitative computed tomography (QCT) in different populations including premenopausal women.[7,8] But no studies have quantified the qualitative bone loss during transmenopause or have demonstrated if this index at the start of transmenopause is suitable for better prediction of bone loss and fracture risk.

Bone turnover markers (BTM) are released into the circulation during bone formation and resorption, providing a real dynamic assessment of skeletal activity. The National Bone Health Alliance working in association with the American Association for Clinical Chemistry has established that the preferred bone resorption and formation markers are the C-terminal telopeptide of type I collagen (CTX) and the bone formation marker N-amino terminal propeptide of type I collagen (PINP), respectively, and have defined the mandatory steps in order to enhance the utility of BTM.[9]

Previous studies have shown that elevated levels of BTM predict higher rates of bone loss and are associated with increase fracture risk independent of BMD.[10–12] However, most of these studies have been performed in postmenopausal women or in older men. In 2010, The US Preventive Services Task Force noted that no study had addressed screening for high risk in the premenopausal or early perimenopausal period.[13] The Study of Women's Health Across the Nation (SWAN) attempted to solve this by studying 2305 premenopausal women, demonstrating that higher levels of NTX and greater increases in NTX during the menopausal transition independently associated with increased fracture risk.[14] However, to our knowledge, there is a lack of prospective studies examining the ability of the principal bone turnover markers (CTX and P1NP) measured at the beginning of transmenopause to predict the subsequent risk of fracture or bone loss.

In summary, as the years immediately previous to the menopause are characterized by accelerated bone loss, it is crucial to identify which women are likely to lose the most bone during the transmenopause. The aims of the present work were to provide a novel approach evaluating the utility of the clinical characteristics, TBS and BTM as potential indicators of bone loss in the transition to menopause.