Choice of lumbar spine bone density reference database for fracture prediction in  men and women: a population-based analysis

William D Leslie; Lisa Langsetmo; Wei Zhou; David Goltzman; Christopher S Kovacs; Jerilynn C Prior; Robert Josse; W P Olszynski; K Shawn Davison; Tassos Anastassiades; Tanveer Towheed; David A Hanley; Kaiser SM; Brian C Lentle; Nancy Kreiger; CaMos Research Group

doi:10.1016/j.jocd.2013.09.003

Bone Health · Bone Mineral Density

Choice of lumbar spine bone density reference database for fracture prediction in men and women: a population-based analysis

Leslie WD, Langsetmo L, Zhou W, Goltzman D, Kovacs CS, Prior J, Josse R, Olszynski WP, Davison KS, Anastassiades T, Towheed T, Hanley DA, Kaiser SM, Lentle B, Kreiger N, CaMos Research Group

Published March 13, 2014 Journal of Clinical Densitometry : the Official Journal of the International Society for Clinical Densitometry, 17(2), 295-300

DOI 10.1016/j.jocd.2013.09.003 PMID 24613388 PMC PMC5094882

Abstract

The diagnosis of osteoporosis in men is controversial, although most studies demonstrate similar fracture rates for men and women with the same level of hip bone mineral density (BMD). Whether this applies to the lumbar spine is currently uncertain and has important implications with respect to choice of reference population for T-score calculation and osteoporosis diagnosis. This question was specifically addressed in the population-based Canadian Multicentre Osteoporosis Study cohort of 4745 women and 1887 men ages 50+ yr at the time of baseline lumbar spine dual energy x-ray absorptiometry. In up to 10 yr of observation, incident clinical major osteoporotic fractures occurred in 110 men (5.8%) vs 543 women (11.4%) (p < 0.001). Mean lumbar spine BMD in men was greater than in women, both among those with and those without incident major osteoporotic fracture (p < 0.001). Men were at slightly lower risk for incident major osteoporotic fracture than women for an equivalent lumbar spine BMD (ageand BMD-adjusted rate ratio 0.75, 95% confidence interval 0.60-0.93, p = 0.008) with similar findings after adjustment for the World Health Organization fracture risk assessment clinical risk factors or competing mortality. No significant sex difference in the BMD relationship was seen for vertebral fractures (clinical or radiographic) or for all fractures. In summary, this large population-based longitudinal cohort study found similar or lower fracture risk for men vs women after adjustment for absolute lumbar spine BMD and additional covariates. The least complicated model for describing fracture risk is therefore to use the same reference lumbar spine data for generating T-scores in men and women.

Topics

Bone Health Bone Mineral Density Measurement

By this author

Luteal Phase · Luteal Phase Deficiency

The influence of the menstrual cycle on muscle injuries - a systematic review and meta-analysis

Guthardt Y et al., 2026 Sci Rep Free full text on PubMed Central

This systematic review and meta-analysis examined the relationship between menstrual cycle phases and the incidence of muscle injuries in female team sport athletes, following PRISMA 2020 and PERSiST guidelines. A comprehensive search was conducted in PubMed, Scopus, and SPORTDiscus from inception to mid-January 2024. Studies were included if they examined female team sport athletes of reproductive age with regular menstrual cycles and compared the occurrence of muscle injuries across at least two menstrual phases. Studies involving hormonal contraceptive use, medications affecting the menstrual cycle or musculoskeletal system, or menstrual dysfunction were excluded. Three studies met the inclusion criteria, involving 318 participants. Meta-analysis yielded a pooled Risk Ratio of 1.18 (95% CI: 0.75 to 1.86, p = 0.46) for injury risk between the luteal and follicular phases, suggesting no statistically significant association. However, the certainty of the cumulative evidence was rated as very low due to methodological limitations, including inconsistent phase classifications and reliance on imprecise methods for identifying menstrual phases. Consequently, no practical or clinical recommendations can be made at this time. Future research employing standardised, physiologically accurate methods for classifying and detecting menstrual cycle phases is necessary to better understand the potential links between hormonal fluctuations and injury risk.

Breast Health · Benign Breast Conditions

MON-154 Breast areolar diameter in healthy menstruating women—a single cycle cross-sectional study of associations with body size and ovulatory characteristics

Baaske AV et al., 2025 Journal of the Endocrine Society Free full text on PubMed Central

Tanner Breast Stage 3 (TB3, at menarche) and Tanner 5 (TB5, once ovulatory cycles established), despite being similar with an “upstanding” nipple, are different. Evidence suggests that steady and high ovulatory-level progesterone exposure accounts for the larger areolar diameter in TB5. Progesterone levels indicate whether the menstrual cycle is ovulatory and have crucial implications for women’s reproductive, metabolic, cardiovascular, and bone health. However, few data show average areolar diameter in regularly cycling women in whom SES, body size, and reproductive variables have been documented. As a step towards better understanding the role of areolar diameter in reflecting estradiol-progesterone balance, this study aims to document the average mean bilateral lateral areolar diameter (AD) in a cohort of regularly menstruating, premenopausal women in whom ovulation was documented in one cycle. We also aim to describe relationships between AD and demographic, anthropometric, and reproductive/ovulation variables. Women were eligible if aged 19-35 years with about month-apart cycles and no exogenous hormone use in the last 3-months. Participants completed one cycle with a daily Menstrual Cycle Diary© (cycle length, CL) and first morning temperatures for Quantitative Basal Temperature© (QBT©) ovulation analysis (normal luteal phase length ≥10 days). Questionnaires gathered SES, ethnic, general health, and reproductive characteristics. Bilateral horizontal areolar diameters were measured by a woman researcher with the participant supine in a warm room. From February 2020 to September 2022 (during the SARS-CoV-2 pandemic), 73 women from Metro Vancouver, British Columbia participated. Women were of median (min-max) age 30 (19-35) years, BMI 24.5 (17.1-41.4) and most identified as White (61.6%) with a median of 16 years of education. Median CL was 29 days (n=65) and QBT data showed 39.3% were normally ovulatory, 34.4% had short luteal phases and 26.2% were anovulatory. Median within-woman bilateral AD was 3.85 (2.35-8.00) cm. Left AD exceeded right (L 3.8 [2.3,8.2]; R 3.7 [ 2.4,7.8]; P=.003). Larger AD (≥3.85cm) was associated with greater body size (BMI r=.534), weight and waist circumference. However, earlier age at menarche (P=.02) was also significantly associated. No other reproductive variables (cycle length, luteal phase length, parity, ever use of CHC) were related to AD before body size adjustments. This study is the first to document, and describe demographic, anthropomorphic and reproductive associations with, AD in community dwelling, regularly cycling, premenopausal women. Future steps will determine the most influential of the anthropometric variables; adjustment for these will facilitate assessments of associations with ovulation related characteristics.

Breast Health · Benign Breast Conditions

SAT-128 Prospective 1-year Menstrual CycleBreast Tenderness and Swelling Experiences—data from healthy regularly cycling women initially proven normally ovulatory on two consecutive cycles

Wood M et al., 2025 Journal of the Endocrine Society Free full text on PubMed Central

Breast tenderness and swelling are associated with premenstrual symptoms but have not been well described in healthy, normally cycling women with known ovulatory status. There are documented negative health risks (in bone, the cardiovascular system and cancers) in association with ovulatory disturbances within normal-length cycles. Identifying breast changes across a predictable, month-apart cycle but with Subclinical Ovulatory Disturbances (SOD, short luteal phase [<10 days] and anovulation (with normal estradiol but lower or absent progesterone levels) could advance our understanding of menstrual cycle physiology, women’s health education and identification of those with chronic SOD who may benefit from cyclic progesterone therapy. Our objective was to determine whether within-woman breast tenderness and swelling experiences differed between normally ovulatory and ovulatory-disturbed cycles. In this 1-year prospective observational study, we examined daily breast tenderness (0-4) and swelling (1-5 change from usual = 3) experiences recorded via the Menstrual Cycle Diary© over ≥8 cycles (mean=13/woman) in 53 women. Ovulatory status was documented by the twice-validated Quantitative Basal Temperature© (QBT©) analysis. Cycle and ovulatory data were previously reported (Prior NEJM, 1990); Diary data were unreported. Participants were healthy, community-dwelling women, mean age 34 (32.4:35.5 years), BMI 22.0, primarily White, and about two-thirds were runners (for health or were marathon-training). Comparison of breast parameters in all normally ovulatory (n = 495) vs all SOD cycles (n = 199) (mean cycle length 28.1 [27.5-28.8 days]), showed significantly higher Breast Tenderness Score [intensity X days; 6.0 (range 1.0, 14.0) vs. 3.0 (0.0, 11.0) (P = .001)] and increased breast size [4.0 (2.0, 4.0) vs. 4.0 (0.0, 4.0) (P = .034]) in normally ovulatory cycles. However, in within-woman analysis (n = 47 women with both normally ovulatory and SOD cycles), breast tenderness/swelling did not significantly differ by ovulatory status. We plotted all ovulatory cycles (n=676) centred on ovulation; this revealed parallel timing of increases in breast tenderness and swelling in the late luteal phase. These 1-year prospective data documented that mild breast tenderness and swelling occurred before flow in cycles with normal ovulation; symptoms were less in SOD cycles. Breast changes were totally absent during the follicular phases.

Hormonal Agents · Progesterone and Progestins

"SUN-109 Feasibility of Cyclic Progesterone and Spironolactone for PCOS-specific Health-Related Quality of Life—a six-month, Phase II, single arm, single center, open-label study"

Nelson K et al., 2025 J Endocr Soc Free full text on PubMed Central

Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder that significantly decreases health-related quality of life (HRQoL). Combined hormonal contraceptives (CHC) are standard-of-care for PCOS but do not mitigate the neuroendocrine cause nor women’s primary concerns. Treatment options need expansion. We hypothesized cyclic oral micronized progesterone (CyclicP4) and spironolactone (Sp) would improve HRQoL, decrease LH, and acne. This Phase II, open-label single-arm pilot study evaluated the 6-month cyclicP4 and Sp treatment feasibility and safety in androgenic PCOS. Our primary outcome was within-woman change in PCOS-HRQoL (PCOSQ). No sample size calculation was possible; 40 was considered feasible. Eligible women were 19-40 years with physician-diagnosed androgenic PCOS. Exclusion criteria included HbA1c > 6.4%, use of metformin or CHC in the last month. Participants received progesterone (300 mg/bedtime 14 days/month); spironolactone (200 mg/day) began in cycle two. Adherence was tracked daily (Menstrual Cycle Diary©) and by pill counts. Safety was assessed by post-study potassium (K+). Feasibility by women’s post-trial treatment intention. PCOSQ, serum LH, calculated bioavailable testosterone (cBAT), HbA1c, hsCRP, and AMH were measured at baseline and trial end. We also assessed perceived acne and sleep changes (-5 to +5), K+ and therapy intent at study end. Six-month change by paired t-test or Wilcoxon signed-rank assessed P < .05 as important. Of 109 expressing interest, 41 enrolled, 36 began therapy (5 did not), and 26 provided final questionnaire data (19 with complete lab data). Completing women were mean age 29 (SD 4.9) years, BMI 30.3 (8.1), 61.5% White and 73.1% with university degrees. Total PCOSQ scores within-woman increased from 3.5±1.0 to 4.9±1.1 (95% CI 3.1-3.8, 4.6-5.3; P<.0000001). Each PCOSQ domain significantly improved (at least P<.001) as did acne and sleep. Weight was unchanged but waist circumference decreased 1.1 cm (NS). LH, cBAT, and AMH each decreased: LH 10.0±5.4 to 8.5±5.2 IU/L (95% CI 7.6-12.3, 6.3-10.8; P<.4), cBAT 0.7±0.4 to 0.6±0.3 nmol/L (0.5-0.9, 0.5-0.8; P<.2), and AMH 10.5±6.5 to 9.7±5.7 ng/ml (7.4-13.7, 7.0-12.4; P<.4). hsCRP remained unchanged (2.8±3.3 to 2.7±3.6 mg/L; P<.8) as did HbA1c (5.2±0.3 to 5.2±0.3%; P<.0). K+ remained within the normal range (3.5-5.0 mmol/L) at final testing (mean 4.0). Two allergic responses to spironolactone and one frequent flow/religious practice led to discontinuation. Feasibility was confirmed and participants strongly preferred continuing therapy (median Likert score=6/7, P<.0001) CyclicP4 and Sp for 6-months was feasible and significantly improved HRQoL in a non-medicine-seeking community women cohort with androgenic PCOS. Though the small sample size limited generalizability, findings are promising. A larger randomized trial comparing CyclicP4 vs. CHC is warranted.

Related research

Bone Mineral Density · Measurement

Using the same bone density reference database for men and women provides a simpler estimation of fracture risk

Langsetmo L et al., 2010 J Bone Miner Res Free full text on PubMed Central

Although low bone mineral density (BMD) predicts fractures, there are postulated sex differences in the fracture "threshold." Some studies demonstrate a higher mean BMD for men with fractures than for women, whereas others note similar absolute risk at the same level of BMD. Our objective was to test the preceding observations in the population-based Canadian Multicentre Osteoporosis Study (CaMOS). We included participants 50+ years of age at baseline. Mean BMD in men was higher than in women among both fracture cases and noncases. Three methods of BMD normalization were compared in age-adjusted Cox proportional hazards models. In a model using the same reference population mean and standard deviation (SD), there were strong effects of age and total-hip BMD for prediction of fractures but no significant effect of sex [hazard ratio (HR) = 0.97, 95% confidence interval (CI) 0.78-1.20] for men versus women. In a model using sex-specific reference means but a common SD, an apparent sex difference emerged (HR = 0.66, 95% CI 0.54-0.81) for men versus women. The sex term in the second model counterbalanced the higher risk introduced by the lower normalized BMD in men. A third model using sex-specific reference means and SDs gave nearly identical results. Parallel results for the three methods of normalization were seen when adjusting for clinical risk factors, excluding antiresorptive users and considering death as a competing risk. We conclude that no adjustment for sex is necessary when using common reference data for both men and women, whereas using sex-specific reference data requires a substantial secondary adjustment for sex.

Bone Mineral Density · Measurement

Associations among disease conditions, bone mineral density, and prevalent vertebral deformities in men and women 50 years of age and older: cross-sectional results from the Canadian Multicentre Osteoporosis Study

Hanley DA et al., 2003 J Bone Miner Res

This cross-sectional cohort study of 5566 women and 2187 men 50 years of age and older in the population-based Canadian Multicentre Osteoporosis Study was conducted to determine whether reported past diseases are associated with bone mineral density or prevalent vertebral deformities. We examined 12 self-reported disease conditions including diabetes mellitus (types 1 or 2), nephrolithiasis, hypertension, heart attack, rheumatoid arthritis, thyroid disease, breast cancer, inflammatory bowel disease, neuromuscular disease, Paget's disease, and chronic obstructive pulmonary disease. Multivariate linear and logistic regression analyses were performed to determine whether there were associations among these disease conditions and bone mineral density of the lumbar spine, femoral neck, and trochanter, as well as prevalent vertebral deformities. Bone mineral density measurements were higher in women and men with type 2 diabetes compared with those without after appropriate adjustments. The differences were most notable at the lumbar spine (+0.053 g/cm2), femoral neck (+0.028 g/cm2), and trochanter (+0.025 g/cm2) in women, and at the femoral neck (+0.025 g/cm2) in men. Hypertension was also associated with higher bone mineral density measurements for both women and men. The differences were most pronounced at the lumbar spine (+0.022 g/cm2) and femoral neck (+0.007 g/cm2) in women and at the lumbar spine (+0.028 g/cm2) in men. Although results were statistically inconclusive, men reporting versus not reporting past nephrolithiasis appeared to have clinically relevant lower bone mineral density values. Bone mineral density differences were -0.022, -0.015, and -0.016 g/cm2 at the lumbar spine, femoral neck, and trochanter, respectively. Disease conditions were not strongly associated with vertebral deformities. In summary, these cross-sectional population-based data show that type 2 diabetes and hypertension are associated with higher bone mineral density in women and men, and nephrolithiasis may be associated with lower bone mineral density in men. The importance of these associations for osteoporosis case finding and management require further and prospective studies.

Osteoporosis · Diagnosis and Treatment

Estimation of the prevalence of low bone density in Canadian women and men using a population-specific DXA reference standard: the Canadian Multicentre Osteoporosis Study (CaMos)

Tenenhouse A et al., 2001 Osteoporos Int

The Canadian Multicentre Osteoporosis Study (CaMos) is a prospective cohort study which will measure the incidence and prevalence of osteoporosis and fractures, and the effect of putative risk factors, in a random sample of 10,061 women and men aged > or = 25 years recruited in approximately equal numbers in nine centers across Canada. In this paper we report the results of studies to establish peak bone mass (PBM) which would be appropriate reference data for use in Canada. These reference data are used to estimate the prevalence of osteoporosis and osteopenia in Canadian women and men aged > or = 50 years. Participants were recruited via randomly selected household telephone listings. Bone mineral density (BMD) of the lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry using Hologic QDR 1000 or 2000 or Lunar DPX densitometers. BMD results for lumbar spine and femoral neck were converted to a Hologic base. BMD of the lumbar spine in 578 women and 467 men was constant to age 39 years giving a PBM of 1.042 +/- 0.121 g/cm2 for women and 1.058 +/- 0.127 g/cm2 for men. BMD at the femoral neck declined from age 29 years. The mean femoral neck BMD between 25 and 29 years was taken as PBM and was found to be 0.857 +/- 0.125 g/cm2 for women and 0.910 +/- 0.125 g/cm2 for men. Prevalence of osteoporosis, as defined by WHO criteria, in Canadian women aged > or = 50 years was 12.1% at the lumbar spine and 7.9% at the femoral neck with a combined prevalence of 15.8%. In men it was 2.9% at the lumbar spine and 4.8% at the femoral neck with a combined prevalence of 6.6%.

Fracture Risk · Risk Factors

Fracture risk prediction: importance of age, BMD and spine fracture status

Krege JH et al., 2013 Bonekey Rep Free full text on PubMed Central

Our purpose was to identify factors for a parsimonious fracture risk assessment model considering morphometric spine fracture status, femoral neck bone mineral density (BMD) and the World Health Organization (WHO) clinical risk factors. Using data from 2761 subjects from the Canadian Multicentre Osteoporosis Study (CaMos), a prospective, longitudinal cohort study of randomly selected community-dwelling men and women aged ⩾50 years, we previously reported that a logistic regression model considering age, BMD and spine fracture status provided as much predictive information as a model considering these factors plus the remaining WHO clinical risk factors. The current analysis assesses morphometric vertebral fracture and/or nonvertebral fragility fracture at 5 years using data from an additional 1964 CaMos subjects who have now completed 5 years of follow-up (total N=4725). Vertebral fractures were identified from lateral spine radiographs assessed using quantititative morphometry at baseline and end point. Nonvertebral fragility fractures were determined by questionnaire and confirmed using radiographs or medical records; fragility fracture was defined as occurring with minimal or no trauma. In this analysis, a model including age, BMD and spine fracture status provided a gradient of risk per s.d. (GR/s.d.) of 1.88 and captured most of the predictive information of a model including morphometric spine fracture status, BMD and all WHO clinical risk factors (GR/s.d. 1.92). For comparison, this model provided more information than a model considering BMD and the WHO clinical risk factors (GR/s.d. 1.74). These findings confirm the value of age, BMD and spine fracture status for predicting fracture risk.

Bone Health › Bone Mineral Density › Measurement

Jerilynn C Prior, Nancy Kreiger

J Prior, N Kreiger

PMID 24613388 24613388 DOI 10.1016/j.jocd.2013.09.003 10.1016/j.jocd.2013.09.003 Leslie et al. 2014, Leslie 2014

Cite this article

Leslie, W. D., Langsetmo, L., Zhou, W., Goltzman, D., Kovacs, C. S., Prior, J., Josse, R., Olszynski, W. P., Davison, K. S., Anastassiades, T., Towheed, T., Hanley, D. A., Kaiser, S. M., Lentle, B., Kreiger, N., & CaMos Research Group (2014). Choice of lumbar spine bone density reference database for fracture prediction in men and women: a population-based analysis. Journal of Clinical Densitometry : the Official Journal of the International Society for Clinical Densitometry, 17(2), 295-300. https://doi.org/10.1016/j.jocd.2013.09.003