Objective: To determine the ability of measurements of bone density in women to predict later fractures. Design: Meta-analysis of prospective cohort studies published between 1985 and end of 1994 with a baseline measurement of bone density in women and subsequent follow up for fractures. For comparative purposes, we also reviewed case control studies of hip fractures published between 1990 and 1994. Subjects: Eleven separate study populations with about 90000 person years of observation time and over 2000 fractures. Main outcome measures: Relative risk of fracture for a decrease in bone mineral density of one standard deviation below age adjusted mean. Results: All measuring sites had similar predictive abilities (relative risk 1.5 (95% confidence interval 1.4 to 1.6)) for decrease in bone mineral density except for measurement at spine for predicting vertebral fractures (relative risk 2.3 (1.9 to 2.8)) and measurement at hip for hip fractures (2.6 (2.0 to 3.5)). These results are in accordance with results of case-control studies. Predictive ability of decrease in bone mass was roughly similar to (or, for hip or spine measurements, better than) that of a 1 SD increase in blood pressure for stroke and better than a 1 SD increase in serum cholesterol concentration for cardiovascular disease. Conclusions: Measurements of bone mineral density can predict fracture risk but cannot identify individuals who will have a fracture. We do not recommend a programme of screening menopausal women for osteoporosis by measuring bone density. Key messages Measuring bone mineral density has been suggested as a method of identifying individuals at high risk of fracture in a preventive context Our meta-analysis of prospective studies showed that all studies measuring bone density at any site had similar predictive ability for a decrease of 1 SD in bone density except for measurements at hip and spine, which have better predictive ability for fractures in hip and spine respectively Predictive ability of decrease in bone mass was roughly similar to (or, for hip or spine measurements, better than) that of a 1 SD increase in blood pressure for stroke and better than a 1 SD increase in serum cholesterol concentration for cardiovascular disease Although bone mineral density measurements can predict fracture risk, they cannot identify individuals who will have a fracture, and a screening programme for osteoporosis cannot be recommended

Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures

Use of high-resolution micro-computed tomography (microCT) imaging to assess trabecular and cortical bone morphology has grown immensely. There are several commercially available microCT systems, each with different approaches to image acquisition, evaluation, and reporting of outcomes. This lack of consistency makes it difficult to interpret reported results and to compare findings across different studies. This article addresses this critical need for standardized terminology and consistent reporting of parameters related to image acquisition and analysis, and key outcome assessments, particularly with respect to ex vivo analysis of rodent specimens. Thus the guidelines herein provide recommendations regarding (1) standardized terminology and units, (2) information to be included in describing the methods for a given experiment, and (3) a minimal set of outcome variables that should be reported. Whereas the specific research objective will determine the experimental design, these guidelines are intended to ensure accurate and consistent reporting of microCT-derived bone morphometry and density measurements. In particular, the methods section for papers that present microCT-based outcomes must include details of the following scan aspects: (1) image acquisition, including the scanning medium, X-ray tube potential, and voxel size, as well as clear descriptions of the size and location of the volume of interest and the method used to delineate trabecular and cortical bone regions, and (2) image processing, including the algorithms used for image filtration and the approach used for image segmentation. Morphometric analyses should be based on 3D algorithms that do not rely on assumptions about the underlying structure whenever possible. When reporting microCT results, the minimal set of variables that should be used to describe trabecular bone morphometry includes bone volume fraction and trabecular number, thickness, and separation. The minimal set of variables that should be used to describe cortical bone morphometry includes total cross-sectional area, cortical bone area, cortical bone area fraction, and cortical thickness. Other variables also may be appropriate depending on the research question and technical quality of the scan. Standard nomenclature, outlined in this article, should be followed for reporting of results.

https://asbmr.onlinelibrary.wiley.com/doi/pdf/10.1002/jbmr.141

Guidelines for assessment of bone microstructure in rodents using micro–computed tomography

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140673602086579.pdf

Epidemiology and outcomes of osteoporotic fractures.

The assessment of vertebral fracture by conventional radiography has been refined and improved using either semiquantitative or quantitative criteria. The inter- and intraobserver variability was determined for a semiquantitative visual approach that we routinely use in clinical studies for assessing prevalent and incident vertebral fractures. In addition, the semiquantitative approach was compared with a quantitative morphometric approach. The incidence and prevalence of vertebral fractures were determined in 57 postmenopausal women (age 65-75 years) by three independent observers. The radiographic basis for fracture definitions and the source of interobserver agreement for the semiquantitative technique. We conclude that the semiquantitative approach can be applied reliably in vertebral fracture assessment when performed using well-defined criteria.

Vertebral fracture assessment using a semiquantitative technique

http://helios.hampshire.edu/~cjgNS/sputtbug/416K/Energy%20Reg/bray2.pdf

Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity.

Five clinical studies of calcium intake, designed with a primary skeletal end point, were reevaluated to explore associations between calcium intake and body weight. All subjects were women, clustered in three main age groups: 3rd, 5th, and 8th decades. Total sample size was 780. Four of the studies were observational; two were cross-sectional, in which body mass index was regressed against entry level calcium intake; and two were longitudinal, in which change in weight over time was regressed against calcium intake. One study was a double-blind, placebo-controlled, randomized trial of calcium supplementation, in which change in weight during the course of study was evaluated as a function of treatment status. Significant negative associations between calcium intake and weight were found for all three age groups, and the odds ratio for being overweight (body mass index, >26) was 2.25 for young women in the lower half of the calcium intakes of their respective study groups (P: < 0.02). Relative to placebo, the calcium-treated subjects in the controlled trial exhibited a significant weight loss across nearly 4 yr of observation. Estimates of the relationship indicate that a 1000-mg calcium intake difference is associated with an 8-kg difference in mean body weight and that calcium intake explains approximately 3% of the variance in body weight.

/pdf/calcium-intake-and-body-weight-4f83xhpjcl.pdf

Calcium intake and body weight.

This study characterized the change in bone mass, bone markers, pituitary/gonadal hormones, vitamin D, parathyroid hormone, and anthropometric variables in a cohort of healthy women as they passed through normal menopause. We recruited 75 women > 46 years old who had premenopausal estradiol (E2) and gonadotropin levels and regular menses. During 9.5 years of observation, 54 experienced normal menopause (PM group) and 21 remained estrogen replete (ER group). Before the beginning of the menopausal drop and after its completion, the slope of bone mass on time in the PM group was 0% for the spine, -0.61% per year for the total body, and -0.45 % per year for the femoral neck. Designating these losses as "age related," there were 0, 4.88, and 3.40% losses for spine, total body bone mineral (TBBM), and femoral neck, respectively, in the 8-year period for which the data were analyzed. Across menopause, we found a sigmoid pattern of bone loss in the PM group beginning about 2-3 years before the last menses and ending about 3-4 years after the last menses. The total estrogen-deprivation bone losses were 10.50, 7.73, and 5.30% for the spine, TBBM, and femoral neck, respectively. In the ER group, we found a 0, 0.59, and 0.93% per year loss in spine, TBBM, and femoral neck, respectively. Serum osteocalcin rose 77%, serum total alkaline phosphatase rose 34%, and urinary hydroxyproline/creatinine (Hypro/Cr) ratio rose 44% in the PM group, while remaining stable in the ER group. We conclude that menopausal bone loss is a composite of loss caused by estrogen deprivation and age per se for the hip and total body, but is caused by estrogen deprivation alone for the spine.

Characterization of perimenopausal bone loss: a prospective study.

Background: Hormone replacement therapy (HRT), the mainstay of osteoporosis prevention, is limited because of dose-related risks, side effects, and patient acceptance. The bone-sparing efficacy and tolerability of the lowest available doses of HRT have not been adequately studied in elderly women. Objective: To determine the bone-sparing effect of continuous low-dose HRT in elderly women. Design: Randomized, double-blind, placebo-controlled trial. Setting: University osteoporosis research and clinical center. Patients: 128 healthy white women (age > 65 years) with low bone mass recruited by word of mouth and by local advertisement. The principal eligibility criterion was spinal bone mineral density of 0.90 g/cm 2 or less. Intervention: Continuous therapy with conjugated equine estrogen, 0.3 mg/d, and medroxyprogesterone, 2.5 mg/d, or matching placebo. Sufficient calcium supplementation was given to bring all calcium intakes above 1000 mg/d in both groups; supplemental oral 25-hydroxyvitamin D was given to maintain serum 25-hydroxyvitamin D levels of at least 75 nmol/L in both groups. Measurements: Bone mineral density of the spine, hip, total body, and forearm; serum total alkaline phosphatase and serum osteocalcin levels at 6-month intervals; and 24-hour urine creatinine and hydroxyproline excretion at baseline, 12 months, and 42 months. Results: During 3.5 years of observation, spinal bone mineral density increased by 3.5% (P < 0.001) in an intention-to-treat analysis and by 5.2% among patients with greater than 90% adherence to therapy. Significant increases were seen in total-body and forearm bone density (P < 0.01). Symptoms related to HRT (breast tenderness, spotting, pelvic discomfort, and mood changes) were mild and short-lived. Conclusions: Continuous low-dose HRT with conjugated equine estrogen and oral medroxyprogesterone combined with adequate calcium and vitamin D provides a bone-sparing effect that is similar or superior to that provided by other, higher-dose HRT regimens in elderly women. This combination is well tolerated by most patients.

The effect of low-dose continuous estrogen and progesterone therapy with calcium and vitamin D on bone in elderly women. A randomized, controlled trial.

Transmenopausal changes in the trabecular bone structure.

Obesity is an increasingly serious health problem in the world. Body mass index (BMI), percentage fat mass, and body fat mass are important indices of obesity. For a sample of pedigrees that contains >10,000 relative pairs (including 1,249 sib pairs) that are useful for linkage analyses, we performed a whole-genome linkage scan, using 380 microsatellite markers to identify genomic regions that may contain quantitative-trait loci (QTLs) for obesity. Each pedigree was ascertained through a proband who has extremely low bone mass, which translates into a low BMI. A major QTL for BMI was identified on 2q14 near the marker D2S347 with a LOD score of 4.04 in two-point analysis and a maximum LOD score (MLS) of 4.44 in multipoint analysis. The genomic region near 2q14 also achieved an MLS >2.0 for percentage of fat mass and body fat mass. For the putative QTL on 2q14, as much as 28.2% of BMI variation (after adjustment for age and sex) may be attributable to this locus. In addition, several other genomic regions that may contain obesity-related QTLs are suggested. For example, 1p36 near the marker D1S468 may contain a QTL for BMI variation, with a LOD score of 2.75 in two-point analysis and an MLS of 2.09 in multipoint analysis. The genomic regions identified in this and earlier reports are compared for further exploration in extension studies that use larger samples and/or denser markers for confirmation and fine-mapping studies, to eventually identify major functional genes involved in obesity.

K. M. Davies

Papers

Calcium intake and body weight.

Characterization of perimenopausal bone loss: a prospective study.

The effect of low-dose continuous estrogen and progesterone therapy with calcium and vitamin D on bone in elderly women. A randomized, controlled trial.

Transmenopausal changes in the trabecular bone structure.

A genomewide linkage scan for quantitative-trait loci for obesity phenotypes.