Fracture risk gradient assessed by categories of bone mineral density and trabecular bone score: the Manitoba BMD Registry.

Trabecular bonescore (TBS) helps to predict fracture risk in older adults. In this registry-based cohort study of patients aged 40 years and older, reduction in bone mineral density (BMD) and TBS are complementary for fracture risk prediction enhancement with lower BMD imparting greater risk than reduction in TBS. PURPOSE: Trabecular bone score (TBS) enhances fracture risk prediction independent of bone mineral density (BMD) in older adults. The purpose of this study was to further evaluate the gradient of fracture risk based on TBS tertile categories and WHO BMD categories, adjusted for other risk factors. METHODS: Using the Manitoba DXA registry, patients aged 40 years and older with spine/hip DXA and L1-L4 TBS were identified. Any incident fractures, major osteoporotic fractures (MOF), and hip fractures were identified. Cox regression models were used to estimate unadjusted and covariate-adjusted hazard ratios (HR, 95%CI) for incident fracture by BMD and TBS category and for each SD decrease in BMD and TBS. RESULTS: The study population included 73,108 individuals, 90% female with mean age 64 years. Mean (SD) minimum T-score was - 1.8 (1.1), and mean L1-L4 TBS was 1.257 (0.123). Lower BMD and TBS, both per SD, by WHO BMD category and by TBS tertile category, were significantly associated with MOF, hip, and any fracture (all HRs p < 0.001). However, the quantum of risk was consistently greater for BMD than TBS, with HRs showing non-overlapping CIs. CONCLUSION: TBS is complementary to BMD in prediction of incident major, hip, and any osteoporosis-related fracture, but reductions in BMD impart greater risk than reductions in TBS on both continuous and categorical scales.

Trabecular bone score in the hip: a new method to examine hip bone microarchitecture-a feasibility study.

Our study found, in older adults who are residents of long-term care facilities, assessing hip microarchitecture with DXA-derived bone texture score may serve as a supplement to bone mineral density to improve fracture prediction and to facilitate decision-making for pharmacological management. PURPOSE: Many patients with high fragility fracture risk do not have a sufficiently low bone mineral density (BMD) to become eligible for osteoporosis treatment. They often have deteriorated bone microarchitecture despite a normal or only mildly abnormal BMD. We sought to examine the beta version of the trabecular bone score (TBS) algorithm for the hip: TBS Hip, an indirect index of bone microarchitecture, and assess if TBS Hip brings complementary information to other bone quality indices such as BMD and bone turnover markers (BTMs) to further improve identifying individuals who are at high risk for fractures. METHODS: In this analysis, we considered baseline TBS Hip at total hip, femoral neck, and greater trochanter, TBS at lumbar spine, BMD at all of these skeletal sites, and BTMs in 132 postmenopausal women who were residents of long-term care (LTC) facilities enrolled in a randomized placebo-controlled osteoporosis clinical trial. RESULTS: On average, participants were 85.2 years old and had a BMI of 26.9 kg/m2. The correlation coefficient between BMD and TBS Hip at total hip, femoral neck, and greater trochanter was 0.50, 0.32, and 0.39 respectively (all p < 0.0001). The correlation coefficient between BMD and lumbar spine TBS was 0.52 (p < 0.0001). There was no statistically significant correlation between BTMs with TBS at lumbar spine or TBS Hip at total hip, femoral neck, and greater trochanter. CONCLUSION: Among older women residing in LTC facilities, there was a moderate correlation between measures of BMD and TBS Hip at total hip, femoral neck, and greater trochanter, suggesting TBS Hip may provide complementary information to BMD .

The Effects of Time-Restricted Eating versus Standard Dietary Advice on Weight, Metabolic Health and the Consumption of Processed Food: A Pragmatic Randomised Controlled Trial in Community-Based Adults.

Weight loss is key to controlling the increasing prevalence of metabolic syndrome (MS) and its components, i.e., central obesity, hypertension, prediabetes and dyslipidaemia. The goals of our study were two-fold. First, we characterised the relationships between eating duration, unprocessed and processed food consumption and metabolic health. During 4 weeks of observation, 213 adults used a smartphone application to record food and drink consumption, which was annotated for food processing levels following the NOVA classification. Low consumption of unprocessed food and low physical activity showed significant associations with multiple MS components. Second, in a pragmatic randomised controlled trial, we compared the metabolic benefits of 12 h time-restricted eating (TRE) to standard dietary advice (SDA) in 54 adults with an eating duration > 14 h and at least one MS component. After 6 months, those randomised to TRE lost 1.6% of initial body weight (SD 2.9, p = 0.01), compared to the absence of weight loss with SDA (-1.1%, SD 3.5, p = 0.19). There was no significant difference in weight loss between TRE and SDA (between-group difference -0.88%, 95% confidence interval -3.1 to 1.3, p = 0.43). Our results show the potential of smartphone records to predict metabolic health and highlight that further research is needed to improve individual responses to TRE such as a shorter eating window or its actual clock time.

Physical and lifestyle factors associated with trabecular bone score values.

TBS is associated with age, weight, childhood physical activity, and BMD in men and age, height, BMD, and mobility in women. INTRODUCTION: Trabecular bone score (TBS) indirectly assesses trabecular microarchitecture at the lumbar spine, providing complementary information to areal BMD. Many studies have investigated the relationships between BMD and lifestyle factors known to affect bone, but such research is limited for TBS. The aim of this study was to assess the relationship between TBS and lifestyle factors in Australian men and women. METHODS: This cross-sectional study involved 894 men and 682 women (ages 24-98 years) enrolled in the Geelong Osteoporosis Study. TBS was assessed by analysis of lumbar spine DXA scans (Lunar Prodigy) using TBS iNsight software (Version 2.2). Bivariate and multivariable linear regression models were used to explore the associations between TBS and physical and lifestyle factors, including anthropometry, alcohol consumption, childhood physical activity, mobility, smoking status, prior low trauma fracture, medication use, and intakes of calcium and vitamin D. RESULTS: In bivariate regression modelling, low mobility and the use of antiresorptive medication were associated with lower TBS in both men and women. Low childhood physical activity was also associated with lower TBS in men. Prior fracture, use of glucocorticosteroids, and total calcium intake were also associated with lower TBS in women. The final adjusted model for men included age, weight, childhood physical activity, and BMD, and for women, age, height, BMD, and mobility. No interaction terms were identified in the models. CONCLUSIONS: Lower TBS is associated with older age, increased weight, low childhood physical activity, and lower BMD in men and older age, shorter stature, lower BMD, and low mobility in women.

The Metabolic Benefits of Menopausal Hormone Therapy Are Not Mediated by Improved Nutritional Habits. The OsteoLaus Cohort.

Menopause alters body composition by increasing fat mass. Menopausal hormone therapy (MHT) is associated with decreased total and visceral adiposity. It is unclear whether MHT favorably affects energy intake. We aimed to assess in the OsteoLaus cohort whether total energy intake (TEI) and/or diet quality (macro- and micronutrients, dietary patterns, dietary scores, dietary recommendations)-evaluated by a validated food frequency questionnaire-differ in 839 postmenopausal women classified as current, past or never MHT users. There was no difference between groups regarding TEI or consumption of macronutrients. After multivariable adjustment, MHT users were less likely to adhere to the unhealthy pattern 'fat and sugar: Current vs. never users [OR (95% CI): 0.48 (0.28-0.82)]; past vs. never users [OR (95% CI): 0.47 (0.27-0.78)]. Past users exhibited a better performance in the revised score for Mediterranean diet than never users (5.00 ± 0.12 vs. 4.63 ± 0.08, p < 0.04). Differences regarding compliance with dietary recommendations were no longer significant after adjustment for covariates. Overall, these results argue against a major role of TEI and diet quality as possible mediators of the MHT metabolic benefits. Future research on this relationship should focus on other potential targets of MHT, such as resting energy expenditure and physical activity.

Reference Ranges for Trabecular Bone Score in Australian Men and Women: A Cross-Sectional Study.

Trabecular bone score (TBS) is a novel method for indirectly assessing trabecular microarchitecture at the lumbar spine, providing information complementary to areal BMD. However, limited reference ranges exist for the normative distribution of TBS, particularly in men. The aim of this study was to develop such a reference range in Australian men and women. This study included 894 men and 682 women (aged 24 to 98 years) enrolled in the Geelong Osteoporosis Study. TBS was determined retrospectively by analysis of lumbar spine DXA scans (Lunar Prodigy) using TBS iNsight software (version 2.2). Multivariable regression techniques were used to determine best-fit models for TBS incorporating age, height, and weight. Age-related differences in TBS were best modelled with a linear relationship in men and a cubic relationship in women. Combined best-fit models for TBS included age and weight in men, and age and height in women. This study provides normative reference ranges for TBS in Australian men and women, and further indicates that TBS may identify individuals at risk for fracture despite normal BMD. © 2018 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

Is trabecular bone score less affected by degenerative-changes at the spine than lumbar spine BMD?

It has been established that degenerative-changes at the spine elevate bone mineral density at the lumbar spine. This study in men reports that trabecular bone score may be less affected by spinal degenerative-changes. PURPOSE: A recent tool for assessing trabecular microarchitecture at the lumbar spine, trabecular bone score (TBS), provides information about bone health complementary to lumbar spine areal BMD (here referred to as BMD). In men, mean BMD increases with increasing age due to degenerative-changes at the spine including osteophytes and aortic calcification. The aim of this study was to investigate whether TBS is similarly affected by the presence of degenerative-changes in men. METHODS: This study included 728 men aged 40-90 years enrolled in the Geelong Osteoporosis Study. Lumbar spine DXA scans (Lunar Prodigy) were used to determine TBS retrospectively (TBS iNsight software, Version 2.2), and for identification of degenerative-changes. Using multivariable regression techniques, the relationships between TBS or BMD and degenerative-changes were assessed, further adjusting for age and weight. The difference between each of the two methods was examined through testing interactions between method, degenerative-changes and age. RESULTS: Of 728 men, 439 (60.3%) were identified as having one or more degenerative-changes at the lumbar spine. Adjusted mean TBS was 1.219 (1.203-1.232) and 1.196 (1.179-1.212) for those with and without degenerative-changes, respectively. Adjusted mean BMD was 1.317 g/cm2 (1.297-1.336) and 1.198 g/cm2 (1.173-1.223) for those with and without degenerative-changes, respectively. Partial r2 for degenerative-changes in the model for TBS was 0.076 and for BMD, 0.257 (both p < 0.05). The three-way interaction between method, degenerative-changes and age was significant (p = 0.05) indicating significant effect of artefacts on the standardised values, affected by age and method. CONCLUSION: This study suggests that TBS is less affected by degenerative-changes at the spine than is BMD. Thus, TBS may prove useful in the assessment of fracture risk in men with degenerative-changes at the spine.

[Use of Trabecular Bone Score as a complementary approach to DXA for fracture risk assessment in clinical practice]. / Trabecular Bone Score en complément à l'absorptiométrie radiologique biphotonique dans l'évaluation du risque fracturaire en routine clinique.

Physicians can assess the risk of fracture based on bone density (BMD) and several risk factors. Some of them and BMD are incorporated into FRAX, an assessment tool that estimates the 10-years probability of fracture. BMD didn't take into account the microarchitecture. TBS is a texture parameter related to bone microarchitecture. A low TBS is associated with a history of fracture and the incidence of new fracture independently of BMD, clinical risk factors and FRAX. TBS is yet integrated in the FRAX tool, and this effect is of greatest utility for individuals who are close to an intervention threshold. It is particularly useful for the evaluation of secondary osteoporosis, including type 2 diabetes, Gluco-corticoïd induced osteoporosis. It responds to osteoporosis treatments and is not influenced by lumbar degenerative disorders.

Les médecins peuvent évaluer le risque fracturaire en se basant sur la densité minérale osseuse (DMO) et des facteurs de risque dont certains ont été intégrés dans l'outil FRAX. Cependant, la microarchitecture n'est pas prise en compte. Le TBS est un indice de texture osseuse lombaire lié à la microarchitecture. Un TBS bas est associé à des antécédents de fracture et à l'incidence de nouvelles fractures, indépendamment de la DMO, des facteurs de risque cliniques et du FRAX. Le TBS a été intégré au FRAX, et son effet est d'autant plus important pour les individus proches du seuil thérapeutique. Le TBS est, en autres, utile pour l'évaluation des ostéoporoses secondaires, notamment le diabète de type 2 et l'ostéoporose cortico-induite. Il réagit aux traitements de l'ostéoporose et n'est pas influencé par les troubles dégénératifs lombaires.

Use of Trabecular Bone Score (TBS) as a Complementary Approach to Dual-energy X-ray Absorptiometry (DXA) for Fracture Risk Assessment in Clinical Practice.

Osteoporosis is a common bone disease characterized by low bone mass and altered bone microarchitecture, resulting in decreased bone strength with an increased risk of fractures. In clinical practice, physicians can assess the risk of fracture for a patient based on several risk factors. Some such as age, weight, and history of fractures after 50 years of age, parental fracture, smoking status, and alcohol intake are incorporated into FRAX, an assessment tool that estimates the 10-year probability of hip fracture and major osteoporotic fractures based on the individual's risk factors profile. The diagnosis of osteoporosis is currently based on bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry scans. Among other widely recognized limitations of BMD is that BMD considers only the density of the bone and fails in measuring bone microarchitecture, for which novel techniques, such as trabecular bone score (TBS), have been developed. TBS is a texture parameter related to bone microarchitecture that may provide skeletal information that is not captured from the standard BMD measurement. Several studies have examined the value of TBS on predicting osteoporotic fractures. Our study aimed to summarize a review of the current scientific literature with focus on fracture risk assessment and to present both its findings and its conclusions regarding how and when TBS should be used. The existing literature indicates that low lumbar spine TBS is associated with a history of fracture and the incidence of new fracture. The effect is largely independent of BMD and of sufficient magnitude to enhance risk stratification with BMD. The TBS effect is also independent of FRAX, with likely greatest utility for those individuals whose BMD levels lie close to an intervention threshold. The clinical and scientific evidence supporting the use of TBS, with the ability of this technology to be seamlessly integrated into a daily workflow, makes TBS an attractive and useful clinical tool for physicians to improve patient management in osteoporosis. Further research is ongoing and necessary to further clarify the role of TBS in additional specific disorders.

Assessing fracture risk in early stage breast cancer patients treated with aromatase-inhibitors: An enhanced screening approach incorporating trabecular bone score.

INTRODUCTION: Aromatase-inhibitors (AIs) are commonly used for treatment of patients with hormone-receptor positive breast carcinoma, and are known to induce bone density loss and increase the risk of fractures. The current standard-of-care screening tool for fracture risk is bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA). The fracture risk assessment tool (FRAX®) may be used in conjunction with BMD to identify additional osteopenic patients at risk of fracture who may benefit from a bone-modifying agent (BMA). The trabecular bone score (TBS), a novel method of measuring bone microarchitecture by DXA, has been shown to be an independent indicator of increased fracture risk. We report how the addition of TBS and FRAX®, respectively, to BMD contribute to identification of elevated fracture risk (EFR) in postmenopausal breast cancer patients treated with AIs. METHODS: 100 patients with early stage hormone-positive breast cancer treated with AIs, no prior BMAs, and with serial DXAs were identified. BMD and TBS were measured from DXA images before and following initiation of AIs, and FRAX® scores were calculated from review of clinical records. EFR was defined as either: BMD ≤-2.5 or BMD between -2.5 and -1 plus either increased risk by FRAX® or degraded microstructure by TBS. RESULTS: At baseline, BMD alone identified 4% of patients with EFR. The addition of FRAX® increased detection to 13%, whereas the combination of BMD, FRAX® and TBS identified 20% of patients with EFR. Following AIs, changes in TBS were independent of changes in BMD. On follow-up DXA, BMD alone detected an additional 1 patient at EFR (1%), whereas BMD+ FRAX® identified 3 additional patients (3%), and BMD+FRAX®+TBS identified 7 additional patients (7%). CONCLUSIONS: The combination of FRAX®, TBS, and BMD maximized the identification of patients with EFR. TBS is a novel assessment that enhances the detection of patients who may benefit from BMAs.

Insights on accelerated skeletal repair in Cushing's disease.

Cushing's disease with prolonged exposure to high circulating levels of glucocorticoids is associated with deterioration of the structural integrity of bone, resulting in increased skeletal fragility and fractures. The mechanism of bone repair following successful surgical treatment is poorly understood. A 34-year-old man presented with a tibial fracture and severely low BMD, elevated AM serum cortisol, ACTH, and 24 h urinary free cortisol, which did not suppress with 2 days of high dose dexamethasone. Following transphenoidal resection of a pituitary microadenoma, serum cortisol and ACTH normalized. A repeat DXA at 8 months post-resection showed no change in BMD, however the Trabecular Bone Score (TBS), which reported severe deterioration of trabecular bone architecture at diagnosis, improved to normal. At that time, teriparatide (TPTD) was given for 2 years, which resulted in a 53.9% increase in BMD with only a small improvement in TBS. In this patient, spontaneous recovery of trabecular bone architecture was reflected by the early correction in TBS. Subsequent TPTD treatment was associated with marked improvement in BMD, presumably due to enhanced mineralization. Complete skeletal repair was achieved by this two-step mechanism in a very short time following successful surgical treatment for Cushing's disease.

Effects of Exemestane and Tamoxifen treatment on bone texture analysis assessed by TBS in comparison with bone mineral density assessed by DXA in women with breast cancer.

We performed an analysis of a substudy of the randomized Tamoxifen Exemestane Adjuvant Multinational trial to determine the effects of exemestane (EXE) and tamoxifen (TAM) adjuvant treatment on bone mineral density (BMD) measured by dual-energy X-ray absorptiometry compared with the trabecular bone score, a novel grey-level texture measurement that correlates with 3-dimensional parameters of bone texture in postmenopausal women with hormone receptor-positive breast cancer for the first time. In total, 36 women were randomized to receive TAM (n = 17) or EXE (n = 19). Patients receiving TAM showed a mean increase of BMD in lumbar spine from baseline of 1.0%, 1.5%, and 1.9% and in trabecular bone score of 2.2%, 3.5%, and 3.3% at 6-, 12-, and 24-mo treatment, respectively. Conversely, patients receiving EXE showed a mean decrease from baseline in lumbar spine BMD of -2.3%, -3.6%, and -5.3% and in trabecular bone score of -0.9%, -1.7%, and -2.3% at 6-, 12-, and 24-mo treatment, respectively. Changes in trabecular bone score from baseline at spine were also significantly different between EXE and TAM: p = 0.05, 0.007, and 0.006 at 6, 12, and 24 mo, respectively. TAM induced an increase in BMD and bone texture analysis, whereas EXE resulted in decreases. The results were independent from each other.

Changing the awareness of low vitamin D status in a rheumatology population: a pre/post-study.

INTRODUCTION: In 2009 hypovitaminosis D was highly prevalent in a population of Swiss rheumatology patients (86%). We aimed to evaluate the evolution of vitamin D status in the same population two years later, after the results of the first study were disseminated to local physicians and patients, in order to determine the evolution of the problem and the impact of physician information. METHOD: Patients in our rheumatology clinic were screened for 25-OH vitamin D. Results were categorised as: deficient (<10 ng/ml or <25 nmol/l), insufficient (10 to 30 ng/ml or 25 to 75 nmol/l) or normal (>30 ng/ml or >75 nmol/l). We also used another cut-off of 20 ng/ml (50 nmol/l). We evaluated the evolution of 25-OH vitamin D dosages and vitamin D3 prescriptions between 2008 and 2011 in our institution and the number of publications on vitamin D in three important medical journals of the French speaking part of Switzerland. RESULTS: Compared with 2009, significantly more patients had normal results in 2011. Fifty-two percent of patients had levels >20 ng/ml in 2009 and 66% in 2011, difference statistically significant (p = 0.001). During the years separating the two study periods the number of 25-OH vitamin D dosages and the prescription of high doses of vitamin D3 increased in our hospital. In addition the number of publications on vitamin D increased between 2008 and 2011. CONCLUSION: We concluded that lower prevalence in hypovitaminosis D is certainly related to better adherence to daily supplements, and to better information and awareness of the physicians about hypovitaminosis D.

High prevalence of hypovitaminosis D in a Swiss rheumatology outpatient population.

Vitamin D is important for bone metabolism and neuromuscular function. While a routine dosage is often proposed in osteoporotic patients, it is not so evident in rheumatology outpatients where it has been shown that the prevalence of hypovitaminosis D is high. The aim of the current study was to systematically evaluate the vitamin D status in our outpatient rheumatology population to define the severity of the problem according to rheumatologic diseases. During November 2009, all patients were offered a screening test for 25-OH vitamin D levels and categorised as deficient (<10 µg/l [ng/ml] [25 nmol/l]), insufficient (10 µg/l to 30 µg/l [25 to 75 nmol/l]) or normal (>30 µg/l [75 nmol/l]). A total of 272 patients were included. The mean 25-OH vitamin D level was 21 µg/l (range 1.5 to 45.9). A total of 20 patients had vitamin D deficiency, 215 patients had an insufficiency and 37 patients had normal results. In the group of patients with osteoporosis mean level of 25-OH vitamin D was 25 µg/l and 31% had normal results. In patients with inflammatory rheumatic diseases (N = 219), the mean level of 25-OH vitamin D was 20.5 µg/l, and only 12% had normal 25-OH vitamin D levels. In the small group of patients with degenerative disease (N = 33), the mean level of 25-OH vitamin D was 21.8 µg/l, and 21% had normal results. Insufficiency and deficiency were even seen in 38% of the patients who were taking supplements. These results confirm that hypovitaminosis D is highly prevalent in an outpatient population of rheumatology patients, affecting 86% of subjects. Despite oral supplementation (taken in 38% of our population), only a quarter of those on oral supplementation attained normal values of 25-OH vitamin D.

Evaluation of the potential use of trabecular bone score to complement bone mineral density in the diagnosis of osteoporosis: a preliminary spine BMD-matched, case-control study.

The trabecular bone score (TBS) is a new parameter that is determined from gray-level analysis of dual-energy X-ray absorptiometry (DXA) images. It relies on the mean thickness and volume fraction of trabecular bone microarchitecture. This was a preliminary case-control study to evaluate the potential diagnostic value of TBS as a complement to bone mineral density (BMD), by comparing postmenopausal women with and without fractures. The sample consisted of 45 women with osteoporotic fractures (5 hip fractures, 20 vertebral fractures, and 20 other types of fracture) and 155 women without a fracture. Stratification was performed, taking into account each type of fracture (except hip), and women with and without fractures were matched for age and spine BMD. BMD and TBS were measured at the total spine. TBS measured at the total spine revealed a significant difference between the fracture and age- and spine BMD-matched nonfracture group, when considering all types of fractures and vertebral fractures. In these cases, the diagnostic value of the combination of BMD and TBS likely will be higher compared with that of BMD alone. TBS, as evaluated from standard DXA scans directly, potentially complements BMD in the detection of osteoporotic fractures. Prospective studies are necessary to fully evaluate the potential role of TBS as a complementary risk factor for fracture.

Interaction between calcium intake and menarcheal age on bone mass gain: an eight-year follow-up study from prepuberty to postmenarche.

Both late menarcheal age and low calcium intake (Ca intake) during growth are risk factors for osteoporosis, probably by impairing peak bone mass. We investigated whether lasting gain in areal bone mineral density (aBMD) in response to increased Ca intake varies according to menarcheal age and, conversely, whether Ca intake could influence menarcheal age. In an initial study, 144 prepubertal girls were randomized in a double-blind controlled trial to receive either a Ca supplement (Ca-suppl.) of 850 mg/d or placebo from age 7.9-8.9 yr. Mean aBMD gain determined by dual energy x-ray absorptiometry at six sites (radius metaphysis, radius diaphysis, femoral neck, trochanter, femoral diaphysis, and L2-L4) was significantly (P = 0.004) greater in the Ca-suppl. than in the placebo group (27 vs. 21 mg/cm(2)). In 122 girls followed up, menarcheal age was recorded, and aBMD was determined at 16.4 yr of age. Menarcheal age was lower in the Ca-suppl. than in the placebo group (P = 0.048). Menarcheal age and Ca intake were negatively correlated (r = -0.35; P < 0.001), as were aBMD gains from age 7.9-16.4 yr and menarcheal age at all skeletal sites (range: r = -0.41 to r = -0.22; P < 0.001 to P = 0.016). The positive effect of Ca-suppl. on the mean aBMD gain from baseline remained significantly greater in girls below, but not in those above, the median of menarcheal age (13.0 yr). Early menarcheal age (12.1 +/- 0.5 yr): placebo, 286 +/- 36 mg/cm(2); Ca-suppl., 317 +/- 46 (P = 0.009); late menarcheal age (13.9 +/- 0.5 yr): placebo, 284 +/- 58; Ca-suppl., 276 +/- 50 (P > 0.05). The level of Ca intake during prepuberty may influence the timing of menarche, which, in turn, could influence long-term bone mass gain in response to Ca supplementation. Thus, both determinants of early menarcheal age and high Ca intake may positively interact on bone mineral mass accrual.