Abstract: Objective: To determine the magnitude and importance of the relation between smoking, bone mineral density, and risk of hip fracture according to age. Design: Meta-analysis of 29 published cross sectional studies reporting the difference in bone density in 2156 smokers and 9705 non-smokers according to age, and of 19 cohort and case-control studies recording 3889 hip fractures reporting risk in smokers relative to non-smokers. Results: In premenopausal women bone density was similar in smokers and non-smokers. Postmenopausal bone loss was greater in current smokers than non-smokers, bone density diminishing by about an additional 2% for every 10 year increase in age, with a difference of 6% at age 80. In current smokers relative to non-smokers the risk of hip fracture was similar at age 50 but greater thereafter by an estimated 17% at age 60, 41% at 70, 71% at 80, and 108% at 90. These estimates of relative risk by age, derived directly from a regression analysis of the studies of smoking and hip fracture, were close to estimates using the difference in bone density between smokers and non-smokers and the association between bone density and risk of hip fracture. The estimated cumulative risk of hip fracture in women in England was 19% in smokers and 12% in non-smokers to age 85; 37% and 22% to age 90. Among all women, one hip fracture in eight is attributable to smoking. Limited data in men suggest a similar proportionate effect of smoking as in women. The association was not explained by smokers being thinner, younger at menopause, and exercising less nor by actions of smoking on oestrogen, but smoking may have a direct action on bone. Conclusions: Hip fracture in old age is a major adverse effect of smoking after the menopause. The cumulative excess bone loss over decades is substantial, increasing the lifetime risk of hip fracture by about half Key messages Smoking has no material effect on bone density in premenopausal women Postmenopausal bone loss is greater in smokers—an additional 0.2% of bone mass each year. The cumulative effect of this over many years is substantial, with a difference of 6% at age 80 In current smokers relative to non-smokers the risk of hip fracture is estimated to be 17% greater at age 60, 41% greater at 70, 71% greater at 80, 108% greater at 90 The data in men are limited but suggest a similar proportionate effect in smokers The cumulative risk of hip fracture to age 85 in women is 19% in smokers and 12% in non-smokers; to age 90 it is 37% and 22% Among all women, one hip fracture in eight is attributable to smoking

Abstract: Background and Methods Osteoporosis is a recognized complication of corticosteroid therapy. Whether it can be prevented is not known. We conducted a 12-month, randomized, placebo-controlled study of intermittent etidronate (400 mg per day for 14 days) followed by calcium (500 mg per day for 76 days), given for four cycles, in 141 men and women (age, 19 to 87 years) who had recently begun high-dose corticosteroid therapy. The primary outcome measure was the difference in the change in the bone density of the lumbar spine between the groups from base line to week 52. Secondary measures included changes in the bone density of the femoral neck, trochanter, and radius and the rate of new vertebral fractures. Results The mean (±SE) bone density of the lumbar spine and trochanter in the etidronate group increased 0.61±0.54 and 1.46±0.67 percent, respectively, as compared with decreases of 3.23±0.60 and 2.74±0.66 percent, respectively, in the placebo group. The mean differences between the groups after one year w...

Abstract: OBJECTIVES: To investigate the effect of milk supplementation on total body bone mineral acquisition in adolescent girls. DESIGN: 18 month, open randomised intervention trial. SUBJECTS: 82 white girls aged 12.2 (SD 0.3) years, recruited from four secondary schools in Sheffield. INTERVENTION: 568 ml (one pint) of whole or reduced fat milk per day for 18 months. MAIN OUTCOME MEASURES: Total body bone mineral content and bone mineral density measured by dual energy x ray absorptiometry. Outcome measures to evaluate mechanism included biochemical markers of bone turnover (osteocalcin, bone alkaline phosphatase, deoxypyridinoline, N-telopeptide of type I collagen), and hormones important to skeletal growth (parathyroid hormone, oestradiol, insulin-like growth factor I). RESULTS: 80 subjects completed the trial. Daily milk intake at baseline averaged 150 ml in both groups. The intervention group consumed, on average, an additional 300 ml a day throughout the trial. Compared with the control group, the intervention group had greater increases of bone mineral density (9.6% v 8.5%, P = 0.017; repeated measures analysis of variance) and bone mineral content (27.0% v 24.1%, P = 0.009). No significant differences in increments in height, weight, lean body mass, and fat mass were observed between the groups. Bone turnover was not affected by milk supplementation. Serum concentrations of insulin-like growth factor I increased in the milk group compared with the control group (35% v 25%, P = 0.02). CONCLUSION: Increased milk consumption significantly enhances bone mineral acquisition in adolescent girls and could favourably modify attainment of peak bone mass.

Abstract: Osteoporosis is now being recognized as a "silent epidemic" and there is an increasing need to improve its diagnosis and management. Quantitative ultrasound (QUS) measurement [broadband ultrasound attenuation (BUA) and velocity] is emerging as an alternative to photon absorptiometry techniques in the assessment of osteoporosis. The fundamental principles governing ultrasound measurements are discussed, and some of the commercially available clinical systems are reviewed, particularly in relation to data acquisition methods. A review of the published in vivo and in vitro data is presented. The general consensus is that ultrasound seems to provide structural information in addition to density. The diagnostic sensitivity of ultrasound measurement of the calcaneus in the prediction of hip fracture has been shown by recent large prospective studies to be similar to hip bone mineral density (BMD) measured with dual-energy X-ray absorptiometry (DXA) and superior to spine BMD. Ultrasound has also been shown to correlate better with the type of hip fracture (intertrochanteric or cervical) than BMD and to provide comparable diagnostic sensitivity to spine BMD in vertebral fractures. It has also been observed that combining the results of both ultrasound and DXA BMD significantly improved hip fracture prediction. Areas where further research is required are identified.

Abstract: In both men and women, a decrease in bone mineral density (BMD) is a major symptom of hypogonadism. Although the effects of estrogens on osteoporosis in women are well documented, comparatively little is known about the effects of long term testosterone substitution on BMD in hypogonadal men. Therefore, we studied BMD in 72 hypogonadal patients (37 men with primary and 35 men with secondary hypogonadism) under testosterone substitution therapy that continued for up to 16 yr. Thirty-two of these men were also seen before initiation of therapy. At annual intervals, trabecular BMD of the lumbar spine was measured by quantitative computed tomography, a true volumetric and reproducible method for long term serial BMD measurements. Serum levels of testosterone increased to the normal range in all androgen-treated hypogonadal men. The most significant increase in BMD was seen during the first year of testosterone treatment in previously untreated patients, when BMD increased from 95.2 +/- 5.9 to 120.0 +/- 6.1 mg/cm3 hydroxyapatite (mean +/- SE). Long term testosterone treatment maintained BMD in the age-dependent reference range in all 72 hypogonadal men, independent of the type of hypogonadism. Transdermal testosterone patches applied to the scrotum were as effective in normalizing BMD as im testosterone enanthate injections. In summary, testosterone therapy increases BMD in hypogonadal men regardless of age. The greatest increase is seen during the first year of treatment in previously untreated patients with low initial BMD. In hypogonadal men, BMD can be normalized and maintained in the normal range by continuous, long term testosterone substitution.

Abstract: The association of height, weight, pubertal stage, calcium intake, and physical activity with bone mineral density (BMD) was evaluated in 500 children and adolescents (205 boys and 295 girls), aged 4-20 yr. The BMD (grams per cm2) of lumbar spine and total body was measured with dual energy x-ray absorptiometry. Lumbar spine volumetric BMD was calculated to correct for bone size. BMD and volumetric BMD increased with age. During puberty, the age-dependent increment was higher. After adjustment for age, the Tanner stage was significantly associated with all three BMD variables in girls and with spinal BMD in boys. In boys, positive correlations were found between BMD and both calcium intake and physical activity after adjustment for age. Stepwise regression analysis with weight, height, Tanner stage, calcium intake, and physical activity as determinants with adjustment for age resulted in a model with Tanner stage in girls and weight in boys for all three BMD variables. The major independent determinant of BMD was the Tanner stage in girls and weight in boys.

Abstract: The material properties of cancellous bone from patients with osteoporosis (OP) or osteoarthritis (OA) were determined and compared with normal controls. Samples were selected from defined sites in human femoral heads which are subjected to different loads in vivo. Overall, OP bone had the lowest stiffness and OA the highest, and this same order was reflected in the apparent densities of the bone, with OA being the most dense and OP the least. Normal and OP bone were found to have very similar stiffness-density relationships and composition. However, OA bone differed significantly from normal. The stiffness of OA bone increased more slowly with apparent density and its material density was significantly reduced. These findings were due to an altered composition of the bone in which the mass fraction of mineral is 12% less than normal. There was also greater site variation of both apparent and material density, suggesting an altered sensitivity to applied load. These results support the concept that osteoporosis is a loss of normal bone. They also provide evidence for the hypothesis that osteoarthritis is, at least partly, a bone disease in which proliferation of defective bone results in an increase in bone stiffness.

Abstract: Prolonged bed rest produces profound changes in muscle and bone, particularly of the lower limb This review first addresses the various models used by researchers to study disuse-induced changes in muscle and bone as observed during prolonged bed rest in humans Dramatic change in muscle mass occurs within 4-6 wk of bed rest, accompanied by decreases of 6 to 40% in muscle strength Immobilization studies in humans suggest that most of this lost muscle mass and strength can be regained with appropriate resistance training within several weeks after a period of disuse Significant decrements in bone mineral density of the lumbar spine, femoral neck, and calcaneus observed in able-bodied men after bed rest are not fully reversed after 6 months of normal weightbearing activity Importantly, the lost bone mass is not regained for some weeks or months after muscle mass and strength have returned to normal, further contributing to the risk of fracture Those who enter a period of bed rest with subnormal muscle and bone mass, especially the elderly, are likely to incur additional risk of injury upon reambulation Practical implications for exercise professionals working with individuals confined to bed rest are discussed

Abstract: The aim of the present experiment was to (i) study the healing after 3 and 7 months of bone defects filled with cancellous bovine bone mineral and (ii) compare the healing around implants placed in normal bone and in defects filled with bovine bone mineral. 5 beagle dogs, about 1-year-old, were used. At baseline, extractions of all mandibular left and right premolars were performed. Bone defects were prepared in the left mandibular quadrant. The defect was immediately filled with natural bovine cancellous bone mineral particles (Bio-Oss, Geistlich Sons Ltd. Wolhusen, Switzerland). No resective surgery was performed in the right jaw quadrant. In both quadrants the flaps were adjusted to allow full coverage of the edentulous ridge and sutured. 3 months later, 2 dogs (group I) were euthanized and biopsies from the premolar regions obtained and prepared for histologic analysis. The 3 remaining dogs (group II) were at this time interval (3 months) subjected to implant installation in the premolar region of both the right and left mandibular jaw quadrants. 2 fixtures of the ITI Dental Implant System (Straumann, Waldenburg, Switzerland; solid-screw; 8 x 3.3 mm) were installed in each side. The fixtures in the test side were placed within the previously grafted defect area, while the fixtures in the control side were placed in normally healed extraction sites. A 4 month period of plaque control was initiated. At the end of this period, a clinical examination including assessment of plaque and soft tissue inflammation was performed and radiographs obtained from the implant sites. Biopsies were harvested and 4 tissue samples were yielded per dog, each including the implant and the surrounding soft and hard peri-implant tissues. The biopsies were processed for ground sectioning or "fracture technique" and the sections produced were subjected to histological examination. The volume of the hard tissue that was occupied by clearly identified Bio-Oss particles was reduced between the 3- and 7-month intervals. This indicates that with time, Bio-Oss becomes integrated and subsequently replaced by newly formed bone. In other words, this xenograft fulfils the criteria of an osteoconductive material. It was also observed that 4 months after implant installation, the titanium/hard tissue interface at test and control sites exhibited, from both a quantitative and qualitative aspect, a similar degree of "osseointegration".

Abstract: OBJECTIVE To examine the association between weight in infancy and bone mass during the seventh decade of life in a population based cohort for which detailed birth and childhood records were preserved. METHODS 189 women and 224 men who were aged 63-73 years and were born in East Hertfordshire underwent bone densitometry by dual energy x ray absorptiometry. Measurements were also made of serum osteocalcin and urinary excretion of type 1 collagen cross linked N-telopeptide. RESULTS There were statistically significant associations between weight at 1 year and bone mineral content (but not bone mineral density) at the spine (P CONCLUSIONS These data confirm our previous observations that growth in infancy is associated with skeletal size in adulthood, and suggest that skeletal growth may be programmed during intrauterine or early postnatal life.

Abstract: BACKGROUND: Reduced bone mineral density in patients with inflammatory bowel disease is thought to be due to disturbances in calcium homeostasis or the effects of corticosteroid treatment. AIMS: To assess the prevalence and mechanism of reduced bone mineral density in 79 patients with inflammatory bowel disease (44 with Crohn's disease, 35 with ulcerative colitis) who did not have significant risk factors for low bone densities. METHODS: Dual x ray absorptiometry was used to measure bone mineral density and serum and urinary markers of osteoblast (alkaline phosphatase, procollagen 1 carboxy terminal peptide and osteocalcin) and osteoclast (pyridinoline, deoxypyridinoline, and type 1 collagen carboxy terminal peptide) activities to assess bone turnover. RESULTS: There was a high prevalence of low bone mineral density (prevalence of T scores < -1.0 from 51%-77%; T scores < -2.5 (osteoporosis) from 17%-28%) with hips being more often affected than vertebrae (p < 0.001). Reduced bone mineral density did not relate to concurrent or past corticosteroid intake, or type, site, or severity of disease. Whereas calcium homeostasis was normal, bone markers showed increased bone resorption without a compensatory increase in bone formation. CONCLUSIONS: The greater prevalence of reduced hip bone mineral density, as opposed to vertebral, mineral density and the pattern of a selective increase in bone resorption contrasts with that found in other known causes of metabolic bone disease.

Abstract: Objective: To determine the relative contribution of decline in bone density to the increase in risk of hip fracture with age in men and women. Design: Incidence data of hip fracture from the general population were combined with the bone density distribution in a sample from the same population and with a risk estimate of low bone density known from literature. Setting: The Netherlands. Subjects: All people with a hospital admission for a hip fracture in 1993, and bone density measured in a sample of 5814 men and women aged 55 years and over in a district of Rotterdam. Main outcome measure: One year cumulative risk of hip fracture by age, sex, and bone density measured at the femoral neck. Results: A quarter of all hip fractures occurred in men. Men reached the same incidence as women at five years older. Controlled for age, the risk of hip fracture by bone density was similar in men and women. The risk of hip fracture increased 13-fold from age 60 to 80; decrease in bone density associated with age contributed 1.9 (95% confidence interval 1.5 to 2.4) in women and 1.6 (1.3 to 1.8) in men. Conclusions: The risk of hip fracture by age and bone density is similar in men and women. The decrease in bone density associated with age makes a limited contribution to the exponential increase of the risk of hip fracture with age. Key messages The risk of hip fracture increases exponentially with age in both men and women Men have about the same risk of hip fracture five years later than women The risk of hip fracture by age and bone density is similar in men and women The difference in age specific incidence is explained completely by the different bone density in men and women The contribution of decline in bone density to the exponential increase in risk of hip fracture with age is relatively small

Abstract: To assess the influence of bone turnover on bone density and fracture risk, we measured serum levels of osteocalcin (OC), bone alkaline phosphatase (BAP), and carboxy-terminal propeptide of type I procollagen (PICP), as well as 24-h urine levels of cross-linked N-telopeptides of type I collagen (NTx) and the free pyridinium cross-links, pyridinoline (Pyd) and deoxypyridinoline (Dpd), among 351 subjects recruited from an age-stratified random sample of Rochester, Minnesota women. PICP, NTx, and Dpd were negatively associated with age among the 138 premenopausal women. All of the biochemical markers were positively associated with age among the 213 postmenopausal women, and the prevalence of elevated turnover (>1 standard deviation [SD] above the premenopausal mean) varied from 9% (PICP) to 42% (Pyd). After adjusting for age, most of the markers were negatively correlated with bone mineral density (BMD) of the hip, spine, or forearm as measured by dual-energy X-ray absorptiometry, and women with osteoporosis were more likely to have high bone turnover. A history of osteoporotic fractures of the hip, spine, or distal forearm was associated with reduced hip BMD and with elevated Pyd. After adjusting for lower BMD and increased bone resorption, reduced bone formation as assessed by OC was also associated with prior osteoporotic fractures. These data indicate that a substantial subset of elderly women has elevated bone turnover, which appears to adversely influence BMD and fracture risk. Combined biochemical and BMD screening may provide better prediction of future fracture risk than BMD alone.

Abstract: Experiments in ob/ob female mice demonstrated that leptin injections not only reduced weight and fat mass, but also restored fertility and partial lactation. To explore factors regulating ob gene expression in reproductive women, we measured serum leptin, body fat, energy expenditure, and milk production in 65 women at 36 weeks of gestation, and at 3 and 6 months postpartum. Serum leptin was measured by solid-phase sandwich enzyme immunoassay, and serum insulin and PRL by solid-phase 125I RIA. Total body water by deuterium dilution, body volume by hydrodensitometry, and bone density by dual-energy x-ray absorptiometry were used to estimate body fat. Serum leptin per unit fat mass was significantly higher at 36 weeks of pregnancy than at 3 and 6 months postpartum (1.25 vs. 0.75, 0.73 ng.mL-1.kg-1). Postpartum normalization of leptin was associated with changes not only in weight and fat mass, but also serum insulin. Leptin was not different between lactating and nonlactating women. Leptin may have affected milk production indirectly through its negative effect on serum PRL. Adjusted for fat-free mass and fat mass, rates of energy expenditure were not significantly correlated with leptin. Our results provide evidence that factors other than fat mass alone modulate serum leptin in reproductive women.

Abstract: We measured the bone mineral density (BMD) at various skeletal sites (total body, hip, anteroposterior [AP] and lateral [lat] spine, and forearm) in a large population-based cohort of women aged 31-89 years (the OFELY cohort), and results were analyzed according to age and postmenopausal years. A significant apparent bone loss was found before the menopause in cancellous bone, i.e., at the lat spine and Ward's triangle (-10%; p < 0.05-0.001). Cross-sectional analysis indicated that, after the menopause, apparent bone loss was accelerated within the 10 years following menopause, continued thereafter at all sites except the AP spine, and was again accelerated in elderly menopausal for more than 25 years. Between 30 and 80 years, BMD decreased by 15 to 44% (T score -1.6 to -3.4) according to the site. The amount of apparent bone loss was highest at the Ward's triangle when expressed in percentage (44%) and at the mid- and distal radius when expressed in number of standard deviations from the peak bone mass (-3.4). As a result, the percentage of women classified as osteoporotic according to the World Heath Organization, i.e., with a T score < or = -2.5, varied substantially from site to site and was highest at the radius (37% and 46%) and lateral spine (25-31%), intermediate at the Ward's triangle, AP spine, and whole body BMD, and lowest at the whole body bone mineral content, femoral neck, and trochanter (10-12%). In conclusion, this cross-sectional but large study suggests that there is a moderate apparent premenopausal bone loss that occurs only at cancellous bone sites and that apparent bone loss is accelerated at most skeletal sites after the age of 75 years. Because of the highly variable coefficient of variation of the peak bone mass at various skeletal sites, the percentage of postmenopausal women identified as being osteoporotic varies widely according to the site of measurement.

Abstract: Background Women may lose bone during lactation because of calcium lost in breast milk. We studied whether calcium supplementation prevents bone loss during lactation or augments bone gain after weaning. Methods We conducted two randomized, placebo-controlled trials of calcium supplementation (1 g per day) in postpartum women. In one trial (the study of lactation), 97 lactating and 99 nonlactating women were enrolled a mean (±SD) of 16±2 days post partum. In the second trial (the study of weaning), 95 lactating women who weaned their infants in the 2 months after enrollment and 92 nonlactating women were enrolled 5.6±0.8 months post partum. The bone density of the total body, lumbar spine, and forearm was measured at enrollment and after three and six months. Results The bone density of the lumbar spine decreased by 4.2 percent in the lactating women receiving calcium and by 4.9 percent in those receiving placebo and increased by 2.2 and 0.4 percent, respectively, in the nonlactating women (P<0.001 for th...

Abstract: Glucocorticoids are potent osteopenic agents, producing negative calcium and bone balance via actions at many sites. The most significant adverse effects of glucocorticoid drugs on the skeleton are probably a direct inhibition of matrix synthesis by the osteoblast, reductions in calcium absorption in both the gut and the renal tubule, and the production of hypogonadism, particularly in men. Reductions in bone density of 10-40% result, the loss being more marked in trabecular bone and in patients receiving a high cumulative dose of the steroid. Fractures occur in about 30% of individuals who take these drugs for an average of 5 years. Bone loss is reversible when glucocorticoid treatment is withdrawn. Bone density can also be increased by sex hormone replacement in those with demonstrable deficiency, by bisphosphonates, and possibly by vitamin D metabolites. All patients treated with glucocorticoids for more than 6 months should be considered for bone densitometry and be offered appropriate drug treatment if values are towards the lower end of the young normal range or if there is already evidence of fractures occurring after minimal trauma. With this approach, the significant morbidity associated with steroid osteoporosis might be substantially avoided.

Abstract: The effect of 12-month dehydroepiandrosterone (DHEA) replacement therapy has been evaluated in 14 60- to 70-yr-old women who received daily applications of a 10% DHEA cream. Vaginal epithelium maturation was stimulated by DHEA administration in 8 of 10 women who had a maturation value of zero at the onset of therapy, whereas a stimulatory effect was also seen in all three women who had an intermediate vaginal maturation index before therapy. The estrogenic effect of DHEA observed in the vagina was not observed in the endometrium, which remained atrophic in all women. Most interesting, the bone mineral density significantly increased at the hip from 0.744 ± 0.021 to 0.759 ± 0.025 g/cm2 after 12 months of treatment (P < 0.05). These changes in bone mineral density were associated with a significant 20.0% decrease (P < 0.01) in plasma bone alkaline phosphatase and a 28% decrease in the urinary hydroxyproline/creatinine ratio. A 2.1-fold increase over the control value (P < 0.01) in plasma osteocalcin was con...

Abstract: Osteoporosis is a skeletal condition characterized by decreased density (mass/volume) of normally mineralized bone. The reduced bone density leads to decreased mechanical strength, thus making the skeleton more likely to fracture. Postmenopausal osteoporosis (Type I) and age-related osteoporosis (Type II) are the most common primary forms of bone loss seen in clinical practice. Secondary causes of osteoporosis include hypercortisolism, hyperthyroidism, hyperparathyroidism, alcohol abuse, and immobilization. In the development of osteoporosis, there is often a long latent period before the appearance of the main clinical manifestation, pathologic fractures. The earliest symptom of osteoporosis is often an episode of acute back pain caused by a pathologic vertebral compression fracture, or an episode of groin or thigh pain caused by a pathologic hip fracture. In the diagnostic process, the extent and severity of bone loss are evaluated and secondary forms of bone loss are excluded. A careful diagnostic work-up that includes clinical history, physical examination, laboratory evaluation, bone densitometry, and radiographic imaging will allow the clinician to determine the cause of osteoporosis and to institute medical interventions that will stabilize and even reverse this frequently preventable condition.

Abstract: PURPOSETo determine the effectiveness and safety of the bisphosphonate risedronate in preventing bone loss in young women with breast cancer and early menopause induced by chemotherapy who are at major risk for the development of postmenopausal osteoporosis.PATIENTS AND METHODSFifty-three white women, aged 36 to 55 years, with breast cancer and artificially induced menopause were stratified according to prior tamoxifen use. Thirty-six patients received tamoxifen (20 mg/d). Within each stratum, patients were randomly assigned to receive risedronate (n = 27) or placebo (n = 26). Treatment consisted of eight cycles oral risedronate 30 mg/d or placebo daily for 2 weeks followed by 10 weeks of no drug (12 weeks per cycle). Patients were monitored for a third year without treatment.RESULTSMain outcomes of the study were changes in lumbar spine and proximal femur (femoral neck, trochanter, and Ward's triangle) bone mineral density (BMD), and biochemical markers of bone turnover. In contrast to a significant decr...

Abstract: Background Bone mass is under strong genetic control, and recent studies in adults have suggested that allelic differences in the gene for the vitamin D receptor may account for inherited variability in bone mass. We studied the relations of the vitamin D–receptor genotype to skeletal development and variation in the size, volume, and density of bone in children. Methods We identified three allelic variants of the vitamin D–receptor gene using the polymerase chain reaction and three restriction enzymes (ApaI, BsmI, and TaqI) in 100 normal prepubertal American girls of Mexican descent. We then determined the relations of the different vitamin D–receptor genotypes (AA, Aa, aa, BB, Bb, bb, TT, Tt, and tt) to the cross-sectional area, cortical area, and cortical bone density of the femoral shaft and the cross-sectional area and density of the lumbar vertebrae. Results The vitamin D–receptor genotype was associated with femoral and vertebral bone density. Girls with aa and bb genotypes had 2 to 3 percent highe...

Abstract: BACKGROUND: Patients with inflammatory bowel disease are at risk of developing metabolic bone disease. AIMS: To compare bone mineral density in patients with Crohn's disease with patients with ulcerative colitis and healthy subjects, and to evaluate possible risk factors for bone loss in inflammatory bowel disease. PATIENTS: 60 patients with Crohn's disease, 60 with ulcerative colitis, and 60 healthy subjects were investigated. Each group consisted of 24 men and 36 women. METHODS: Lumbar spine, femoral neck, and total body bone mineral density were measured by dual x ray absorptiometry (DXA), and Z scores were obtained by comparison with age and sex matched normal values. RESULTS: Mean Z scores were significantly lower in patients with Crohn's disease compared with patients with ulcerative colitis and healthy subjects. Patients with ulcerative colitis had bone mineral densities similar to healthy subjects. Use of corticosteroids, body mass index (BMI), and sex were significant predictor variables for bone mineral density in Crohn's disease. In ulcerative colitis only body mass index and sex were of significant importance. Disease localisation and small bowel resections had no influence on bone mineral density in patients with Crohn's disease. CONCLUSIONS: Patients with Crohn's disease have reduced bone mineral density. Several factors are probably involved, but the reduction is associated with corticosteroid therapy. When studying skeletal effects of inflammatory bowel disease, patients with Crohn's disease and those with ulcerative colitis should be evaluated separately.

Abstract: Background: The efficacy of antiresorptive therapy in preventing fractures in women at highest fracture risk, such as very elderly women or those with severe osteoporosis, is uncertain. Participants and Methods: Using data from a doubleblind, randomized, placebo-controlled clinical trial that enrolled 2027 postmenopausal women aged 55 to 81 years with low femoral neck bone mineral density (BMD) and existing vertebral fractures, we examined the consistency of the effect of treatment with alendronate sodium in preventing fractures within a priori-specified risk subgroups defined at baseline by age, bone density, number of preexisting vertebral fractures, and history of postmenopausal fracture. The women were randomized to oral administration of alendronate or placebo and followed up for an average of 2.9 years. The initial dose of alendronate sodium was 5 mg/d; the dosage was increased from 5 to 10 mg/d at 24 months. New vertebral fractures, the primary end point of this arm of the trial, were defined by morphometry as a decrease of 20% and at least 4 mm in any vertebral height between baseline and a follow-up radiograph at 36 months. Incident clinical fractures, the secondary end point, included nonspine and clinical (symptomatic) vertebral fractures. All clinical fractures were confirmed with x-ray film reports or, in the case of clinical vertebral fractures, x-ray films. Results: Overall, there was a 47% significant reduction in risk of new vertebral fractures in the alendronate group compared with the placebo group. The reduction in risk of new vertebral fracture was consistent across fracture risk categories including age (relative risk [RR], 0.49 in women 2 [median] compared with 0.53 in those with a BMD ≥0.59 g/cm 2 ), and number of preexisting vertebral fractures (RR, 0.58 in women with 1 vertebral fracture compared with 0.52 in those with ≥2). The overall significant 28% reduction in risk of incident clinical fractures in the alendronate group compared with the placebo group was also observed within these subgroups. Compared with the number of lower-risk women, a similar or smaller number of high-risk women needed to be treated to prevent 1 fracture. For example, 8 women aged 75 years or older compared with 9 women younger than 75 years, or 4 women with 2 or more existing vertebral fractures compared with 16 women with 1 existing vertebral fracture, needed to be treated with alendronate for 5 years to prevent 1 new vertebral fracture. Conclusions: Alendronate effectively reduces fracture risk in postmenopausal women with vertebral fractures and low BMD, including those women at highest risk because of advanced age or severe osteoporosis. Since the risk reductions observed with alendronate treatment were consistent within fracture risk categories, more fractures were prevented by treating women at highest risk. Arch Intern Med. 1997;157:2617-26244

Abstract: OBJECTIVE—To determine the material properties of the subchondral bone plate in patients with osteoarthritis or osteoporosis. METHODS—Femoral heads were obtained after surgical removal from age and sex matched groups of patients with either osteoporosis (OP), after a fractured neck of femur, or osteoarthritis (OA) and compared with a normal group. The mechanical stiffness, density, and composition of the subchondral bone plate from sites selected to represent areas of heavy, intermittent, and light loading were measured. RESULTS—Overall, OP bone was the least stiff and dense, followed by OA bone; normal bone was stiffer and more dense (p < 0.05). Though OP bone contained less mineral, the organic and water contents were increased in proportion suggesting no change in the relative amount of organic matrix. OA bone was also hypomineralised (p < 0.05) but had different organic and water fractions suggesting a defect in the matrix. Site variation of most properties was small, though across all the groups the superior region was significantly stiffer than the inferior. CONCLUSION—This study shows that subchondral bone plate is less stiff than normal in both OP and OA and so cannot, by itself, explain the preserving of the overlying cartilage in OP while aiding its destruction in OA. However, the subchondral bone plate is only one part of the bony structure of the femoral head and changes in the cancellous bone need to be considered. The generalised changes in bone composition found in patients with OA support the hypothesis that the disease could involve the bone in the primary pathogenesis.

Abstract: Adults with childhood onset GH deficiency (GHD) have reduced bone mass, increased fat mass, and disorders of lipid metabolism. The aim of the present study was to evaluate bone mineral density (BMD), bone metabolism, body composition, and lipid metabolism in GHD children before and during 2-3 yr of GH treatment (GHRx). Forty children with GHD, mean age 7.9 yr, participated in the study of bone metabolism and body composition; and an additional group of 17 GHD children, in the study of lipid metabolism. Lumbar spine BMD, total body BMD, and body composition were measured with dual-energy x-ray absorptiometry. Volumetric BMD (bone mineral apparent density, BMAD) was calculated to correct for bone size. BMD, BMAD, lean tissue mass, bone mineral content, fat mass, and percentage body fat were expressed as SD scores (SDS), in comparison with normative data of the same population. Lumbar spine BMD and BMAD and total body BMD were all decreased at baseline. All BMD variables increased significantly during GHRx, lumbar spine BMD SDS, already after 6 months of treatment. Lean tissue mass SDS increased continuously. Bone mineral content SDS started to increase after 6 months GHRx. Fat mass SDS decreased during the first 6 months of GHRx and remained stable thereafter. Biochemical parameters of bone formation and bone resorption did not differ from normal at baseline and increased during the first 6 months of GHRx. Serum 1,25 dihydroxyvitamin D increased continuously during GHRx, whereas PTH and serum calcium remained stable. Lipid profile was normal at baseline: Atherogenic index had decreased and apolipoprotein A1(Apo-A1) had increased after 3 yr of treatment. In conclusion, children with GHD have decreased bone mass. BMD, together with height and lean tissue mass, increased during GHRx. GHRx had a beneficial effect on lipid metabolism.