Comparison of Bone Tissue Elements Between Normal and Osteoarthritic Pelvic Bones in Dogs.

Physiochemical analysis of bones affected with osteoarthritis (OA) can be used to better understand the etiology of this disease. We investigated the percentage of chemical elements in canine pelvic bone affected with varying degrees of OA using a handheld X-ray fluorescence (XRF) analyzer that discriminates magnesium (Mg(12)) through bismuth (Bi(83)). A total of 45 pelvic bones, including both ilium and subchondral acetabular bone plates, were categorized as normal (n = 20), mild grade OA (n = 5), moderate grade OA (n = 15), and severe grade OA (n = 5). In normal pelvic, seven elements (P, Ca, Mn, Ag, Cd, Sn, and Sb) differed (p < 0.005) in percentage between ilium and acetabulum. Comparisons among the four OA groups found Mn and Fe to be highest in severe grades (p < 0.05) in both ilium and acetabulum. Three heavy metals (Ag, Sn, and Sb) were detected in high percentages (p < 0.05) in the severe OA group in the acetabulum, but in ilium only Sn was high (p < 0.05) in severe OA. In conclusion, the percentages of several elements differed between pelvic types in dogs, and also with increasing severity of OA. The finding of high Mn and Fe in severe grade OA bone suggests these two elements may be useful in future studies of the etiology and pathophysiology of OA.

Blood Cadmium Is Associated with Osteoporosis in Obese Males but Not in Non-Obese Males: The Korea National Health and Nutrition Examination Survey 2008-2011.

Osteoporosis in males is becoming an important health concern in an aging society. The aim of this study was to investigate the associations between cadmium exposure and osteoporosis by considering the effect of obesity in aged males using a representative sample of the Korean population. Using the fourth and fifth Korea National Health and Nutrition Examination Survey data, 1098 males over 50 years of age were analyzed. The blood cadmium concentration was measured. The bone mineral density in the total hip, femur neck, and lumbar spine was measured using dual-energy X-ray absorptiometry. T-scores to determine the presence of osteoporosis were calculated using a Korean reference. Subjects were stratified into two groups according to obesity status (body mass index <25 kg/m² and ≥25 kg/m²). In comparison with obese subjects with blood cadmium <1.00 µg/L, those with blood cadmium >1.50 µg/L had odds ratios of 4.57 (95% confidence interval [CI] 1.49-14.01) and 5.71 (95% CI 1.99-16.38) at the femur neck and any site, respectively, after adjusting for potential confounders such as age, serum creatinine, vitamin D deficiency, smoking, alcohol drinking, and physical activity level. However, this association was not significant in non-obese males. In conclusion, the effect of cadmium on osteoporosis was different by obesity status in aged males.

Composition and functionality of bone affected by dietary glycated compounds.

Our aim was to investigate the effects of Maillard reaction products (MRPs) from bread crust (BC) on bone composition and its mechanical properties, determining whether any such effects are related to the molecular weight of different MRPs. For 88 days after weaning rats were fed a control diet or diets containing BC, or its soluble low molecular weight (LMW), soluble high molecular weight (HMW) or insoluble fractions. Animals' food consumption and body weights were monitored. After sacrifice, the femur, pelvic bone and tibia were removed for composition, physical and biomechanical properties analysis. It was found that body and femur weights, density, volume and organic matrix decreased, whereas pentosidine increased after consumption of experimental diets, especially in the HMW and insoluble groups (104.7 and 102.9 mmol mol(-1) collagen) vs. the control group (41.7 mmol mol(-1) collagen). Bone stiffness fell by 50% in the LMW, HMW and insoluble groups and failure load and energy to failure tended to decrease in the same animals after MRPs intake. Consumption of diets containing assayed MRPs during growth leads to lower bone size and introduces some changes in its mechanical behavior which appear to be related to an increase in the pentosidine level of bone.

The relationship between bisphosphonate adherence and fracture: is it the behavior or the medication? Results from the placebo arm of the fracture intervention trial.

Medication compliance may be a surrogate for factors that improve health outcomes such as fractures. Little is known about the size of this potential "healthy adherer" effect. We evaluated the hypothesis that compliance with placebo is associated inversely with bone loss and fractures among women participating in the Fracture Intervention Trial (FIT). Compliance with placebo and alendronate was evaluated using daily medication diaries. Women were defined as having high compliance if they took 80% or more of dispensed study medication. Change in bone mineral density (BMD) was assessed using mixed models comparing women with high versus lower compliance with placebo. Cox proportional-hazards models analyzed the association between placebo compliance and various types of fractures. Among 3169 women randomized to placebo, 82% had high compliance. Compared with women with lower placebo compliance, bone loss at the total hip was lower in compliant placebo-treated women (-0.43%/year versus -0.58%/year, p = .04). Among placebo-treated women, there were 46 hip, 110 wrist, 77 clinical vertebral, and 492 total clinical fractures. Compared with women with lower placebo compliance, women with high placebo compliance had a nonsignificant reduced risk for hip fracture [adjusted hazard ratio (HR) = 0.67, 95% confidence interval (CI) 0.30-1.45]. This trend was not observed for other fractures. Medication compliance may be a proxy for factors that confers benefit on reducing hip fracture (but not other types of fractures) independent of the effect of the medication itself. Nonrandomized studies of interventions designed to maintain or improve bone density and/or hip fracture may need to consider medication compliance as a confounder to better estimate true intervention effects.

Bone-cement interfacial behaviour under mixed mode loading conditions.

Interfacial behaviour of the bone-cement interface has been studied under tensile, shear and mixed mode loading conditions. Bovine cancellous bone was used to bond with acrylic bone cement to form bone-cement interface samples, which were mechanically tested under selected tensile, shear and mixed mode loading conditions. The influence of the loading angle and the extent of the cement penetration on the interfacial behaviour were examined. The failure mechanisms with regard to loading mode were examined using micro-focus computed tomography. The measured tensile and shear responses were utilized in a cohesive zone constitutive model, from which the pre-yield linear and the post-yield exponential strain softening behaviour under mixed mode loading conditions was predicted. The implications of the work on the studies of cemented joint replacements are also discussed.

Effect of soy isoflavone extract supplements on bone mineral density in menopausal women: meta-analysis of randomized controlled trials.

This study was conducted to clarify the effect of ingesting soy isoflavone extracts (not soy protein or foods containing isoflavones) on bone mineral density (BMD) in menopausal women. PubMed, CENTRAL, ICHUSHI, CNKI, Wanfang Data, CQVIP, and NSTL were searched for randomized controlled trials published in English, Japanese, or Chinese reporting the effects of soy isoflavone extracts on lumbar spine or hip BMD in menopausal women. Trials were identified and reviewed for inclusion and exclusion eligibility. Data on study design, participants, interventions, and outcomes were extracted. Eleven, seven, five, and five trials were finally selected for estimation of the effects on spine, femoral neck, hip total, and trochanter BMD, respectively. Meta-analysis including data from1240 menopausal women revealed that daily ingestion of an average of 82 (47-150) mg soy isoflavones (aglycone equivalent) for 6-12 months significantly increased spine BMD by 22.25 mg/cm2 (95% CI: 7.62, 32.89; p=0.002), or by 2.38% (95% CI: 0.93, 3.83; p=0.001) compared with controls (random-effects model). Subgroup analyses indicated that the varying effects of isoflavones on spine BMD across trials might be associated with study characteristics of intervention duration (6 vs. 12 months), region of participant (Asian vs. Western), and basal BMD (normal bone mass vs. osteopenia or osteoporosis). No significant effects on femoral neck, hip total, and trochanter BMD were found. Soy isoflavone extract supplements increased lumbar spine BMD in menopausal women. Further studies are needed to address factors affecting the magnitudes of effect on spine and to verify the effect on hip.

Gene-gene interactions in RANK/RANKL/OPG system influence bone mineral density in postmenopausal women.

Receptor activator of nuclear factor kappaB (RANK) is one of the proteins in regulation of osteoclastogenesis via RANK/RANKL/OPG. Gene that codes for RANK protein (TNFRSF11A) was associated with osteoporotic fractures in a recent genome-wide association study. As variations in the RANK gene could alter its expression and activity, the aim of our study was to evaluate the influence of four RANK gene polymorphisms on bone mineral density (BMD) and biochemical markers. We evaluated 467 postmenopausal women and 117 elderly men. All subjects were genotyped for the presence of RANK polymorphisms -670G>C, +34694C>T, +34901G>A and +35966insdelC. BMD and biochemical markers were measured. Significant associations of +35966insdelC with BMD at lumbar spine (BMD-ls), total hip (BMD-th) and femoral neck (BMD-fn) were found in postmenopausal women (p=0.020, 0.024 and 0.034), but not in men. Significant gene-gene interaction was proved for two RANK polymorphisms in combination with OPG and RANKL polymorphisms studied previously in postmenopausal women. Firstly, RANK/RANKL (+34901G>A/-290C>T) combination was associated with BMD-fn, BMD-th and BMD-ls (p=0.034, 0.016 and 0.050), and secondly, RANK/OPG combination (+35966insdelC/K3N) showed influence on BMD-fn and BMD-ls (p=0.043 and 0.039). Our results suggest that gene-gene interactions between RANK and OPG, and RANK and RANKL influence BMD in postmenopausal women.

Unipedal standing exercise and hip bone mineral density in postmenopausal women: a randomized controlled trial.

The aim of this study was to test the effect of unipedal standing exercise on bone mineral density (BMD) of the hip in postmenopausal women. Japanese postmenopausal women (n = 94) were assigned at random to an exercise or control group (no exercise). The 6-month exercise program consisted of standing on a single foot for 1 min per leg 3 times per day. BMD of the hip was measured by dual-energy X-ray absorptiometry. There was no significant difference in age and baseline hip BMD between the exercise group (n = 49) and control group (n = 45). Exercise did not improve hip BMD compared with the control group. Stepwise regression analysis identified old age as a significant determinant (p = 0.034) of increased hip total BMD at 6 months after exercise. In 31 participants aged >/=70 years, the exercise group (n = 20) showed significant increase in the values of hip BMD at the areas of total (p = 0.008), intertrochanteric (p = 0.023), and Ward's triangle (p = 0.032). The same parameters were decreased in the control group (n = 11). The percent changes in hip BMD of the exercise group were not significantly different from those of the control group either in the participants with low baseline hip total BMD (<80% of the young adult mean) or high baseline hip total BMD (> or =80% of the young adult mean). In conclusion, unipedal standing exercise for 6 months did not improve hip BMD in Japanese postmenopausal women. Effect of exercise on hip total BMD was age dependent. In participants aged > or =70 years, the exercise significantly increased hip total BMD.

The efficacy and tolerability of once-weekly alendronate 70 mg on bone mineral density and bone turnover markers in postmenopausal Chinese women with osteoporosis.

Osteoporosis has become an important health problem in postmenopausal Chinese women. Bisphosphonates currently are the preferred therapy for treating osteoporosis. However, the use of daily regimen of alendronate in women at risk for osteoporosis has been relatively low in China because of its dosing inconvenience. To determine the efficacy and tolerability of once-weekly alendronate 70 mg in Chinese, a multicenter, randomized, double blind, placebo controlled study was performed in China. Five hundred and sixty postmenopausal women (< or =85 years old) with osteoporosis were randomly assigned to receive either alendronate 70 mg or placebo once-weekly for 12 months. All women received calcium 500 mg daily and vitamin D 200 IU daily. A significant increase in lumbar spine BMD was already evident at 6 months of alendronate treatment (P < 0.001). The alendronate group showed significant increase (P < 0.001) in BMD at 12 months at both the spine and hip when compared with the placebo group (lumbar spine 4.87% vs. 0.4%, femoral neck 2.47% vs. 0.31%, trochanter 3.24% vs. 0.78%, total hip 2.56% vs. 0.28%, respectively). The percentage of women with > or =0% and > or =3% BMD increase in lumbar spine was significantly greater in women with alendronate than placebo (P < 0.001). Significant reduction in urine N-telopeptide (NTx) and serum bone-specific alkaline phosphatase were evident at 6 and 12 months, respectively, with alendronate treatment. No significant differences in the incidence of adverse experiences and upper gastrointestinal adverse experiences were seen. We conclude that once-weekly alendronate 70 mg is an effective and well-tolerated agent for the treatment of postmenopausal osteoporosis in Chinese women.

Decreased bone mineral density in men with metabolic syndrome alone and with type 2 diabetes.

BACKGROUND: Metabolic syndrome is associated with decreased physical activity and increased incidence of diabetes. Bone Mineral density (BMD) is positively associated with physical activity. Lower BMD is a risk factor for bone fractures. Whether subjects with metabolic syndrome alone show early signs of lower BMD and osteoporosis similar to those present in diabetic is not known. MATERIAL/METHODS: This cross-sectional study in male veterans examined the BMD in 3458 non-diabetic men and 735 men with type 2 diabetes. In addition, the BMD changes in non-diabetic men without any metabolic syndrome were compared with non-diabetic men with metabolic syndrome as established by the criteria of the Adult Treatment Panel III. RESULTS: BMD of hip was significantly lower and incidence of osteoporosis higher in diabetic subjects compared with age and body mass index (BMI) matched non-diabetic subjects. BMD of AP spine was significantly higher in diabetic subjects compared with non-diabetics but similar when subjects were matched for BMI. Men with metabolic syndrome alone had higher osteoporosis and lower BMD of hip compared with those without metabolic syndrome. CONCLUSIONS: The BMD of hip is lower in diabetics compared with age and BMI-matched non-diabetic men, and its level is similar in age and BMI-matched diabetics and non-diabetic men with metabolic syndrome. This suggests that both diabetes and metabolic syndrome are associated independently with higher osteoporosis and lower BMD of hip and are risk factors for increased incidence of hip fractures in men.

Contribution of trochanteric soft tissues to fall force estimates, the factor of risk, and prediction of hip fracture risk.

UNLABELLED: We compared trochanteric soft tissue thickness, femoral aBMD, and the ratio of fall force to femoral strength (i.e., factor of risk) in 21 postmenopausal women with incident hip fracture and 42 age-matched controls. Reduced trochanteric soft tissue thickness, low femoral aBMD, and increased ratio of fall force to femoral strength (i.e., factor of risk) were associated with increased risk of hip fracture. INTRODUCTION: The contribution of trochanteric soft tissue thickness to hip fracture risk is incompletely understood. A biomechanical approach to assessing hip fracture risk that compares forces applied to the hip during a sideways fall to femoral strength may by improved by incorporating the force-attenuating effects of trochanteric soft tissues. MATERIALS AND METHODS: We determined the relationship between femoral areal BMD (aBMD) and femoral failure load in 49 human cadaveric specimens, 53-99 yr of age. We compared femoral aBMD, trochanteric soft tissue thickness, and the ratio of fall forces to bone strength (i.e., the factor of risk for hip fracture, phi), before and after accounting for the force-attenuating properties of trochanteric soft tissue in 21 postmenopausal women with incident hip fracture and 42 age-matched controls. RESULTS: Femoral aBMD correlated strongly with femoral failure load (r2 = 0.73-0.83). Age, height, and weight did not differ; however, women with hip fracture had lower total femur aBMD (OR = 2.06; 95% CI, 1.19-3.56) and trochanteric soft tissue thickness (OR = 1.82; 95% CI, 1.01, 3.31). Incorporation of trochanteric soft tissue thickness measurements reduced the estimates of fall forces by approximately 50%. After accounting for force-attenuating properties of trochanteric soft tissue, the ratio of fall forces to femoral strength was 50% higher in cases than controls (0.92 +/- 0.44 versus 0.65 +/- 0.50, respectively; p = 0.04). CONCLUSIONS: It is possible to compute a biomechanically based estimate of hip fracture risk by combining estimates of femoral strength based on an empirical relationship between femoral aBMD and bone strength in cadaveric femora, along with estimates of loads applied to the hip during a sideways fall that account for thickness of trochanteric soft tissues. Our findings suggest that trochanteric soft tissue thickness may influence hip fracture risk by attenuating forces applied to the femur during a sideways fall and provide rationale for developing improved measurements of trochanteric soft tissue and for studying a larger cohort to determine whether trochanteric soft tissue thickness contributes to hip fracture risk independently of aBMD.

Vitamin D receptor 3' haplotypes are unequally expressed in primary human bone cells and associated with increased fracture risk: the MrOS Study in Sweden and Hong Kong.

UNLABELLED: The VDR is a prime candidate gene for osteoporosis. Here, we studied three common VDR haplotypes in relation to bone phenotypes in 5014 participants of the global MrOS Study. We also studied the relative expression of the haplotypes in human bone cells. One haplotype was associated with increased fracture risk and differently expressed in primary human bone cells. INTRODUCTION: Vitamin D plays an essential role in skeletal metabolism by binding to its nuclear steroid receptor, the vitamin D receptor (VDR). The heritability of BMD is well established, and the VDR gene is considered a prime candidate suggested to partially account for genetically controlled BMD variance in the population. MATERIALS AND METHODS: Here, we reconstructed common haplotypes in the VDR 3' untranslated region (UTR) and studied the association to BMD and risk of vertebral fractures in elderly men from Sweden (n = 3014) and Hong Kong (n = 2000), all participants of the global MrOS Study. To assess any functional implications of the VDR polymorphisms, we studied allele-specific expressions of the different VDR 3' UTR haplotypes in the normal chromosomal context of 70 unrelated human trabecular bone samples. This was performed by quantitative genotyping of coding polymorphisms in RNA samples and in corresponding DNA samples isolated from the bone samples. RESULTS: Three major haplotypes were reconstructed and in agreement with the previously well-defined baT, BAt, and bAT haplotypes, herein denoted Hap1, Hap2, and Hap3. The Hap1 haplotype was independently associated with increased risk of vertebral fractures in Swedish men (OR, 1.655; 95% CI, 1.146-2.391; p < 0.01) and with lower lumbar spine BMD in elderly men from Sweden (p < 0.01) and Hong Kong (p < 0.05). The VDR gene was also shown to exhibit a 3' UTR haplotype dependent allelic imbalance, indicating that the VDR Hap1 allele was overexpressed in human trabecular bone samples. CONCLUSIONS: The results indicate that the relatively overexpressed VDR Hap1 haplotype could be considered a risk allele for osteoporosis regardless of ethnicity.

Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis.

UNLABELLED: Oral daily (2.5 mg) and intermittent ibandronate (between-dose interval of >2 months), delivering a similar cumulative exposure, were evaluated in 2946 osteoporotic women with prevalent vertebral fracture. Significant reduction in incident vertebral fracture risk by 62% and 50%, respectively, was shown after 3 years. This is the first study to prospectively show antifracture efficacy for the intermittent administration of a bisphosphonate. INTRODUCTION: Bisphosphonates are important therapeutics in postmenopausal osteoporosis. However, they are currently associated with stringent dosing instructions that may impair patient compliance and hence therapeutic efficacy. Less frequent, intermittent administration may help to overcome these deficiencies. This study assessed the efficacy and safety of oral ibandronate administered either daily or intermittently with a dose-free interval of >2 months. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled, parallel-group study enrolled 2946 postmenopausal women with a BMD T score < or = -2.0 at the lumbar spine in at least one vertebra (L1-L4) and one to four prevalent vertebral fractures (T4-L4). Patients received placebo or oral ibandronate administered either daily (2.5 mg) or intermittently (20 mg every other day for 12 doses every 3 months). RESULTS AND CONCLUSIONS: After 3 years, the rate of new vertebral fractures was significantly reduced in patients receiving oral daily (4.7%) and intermittent ibandronate (4.9%), relative to placebo (9.6%). Thus, daily and intermittent oral ibandronate significantly reduced the risk of new morphometric vertebral fractures by 62% (p = 0.0001) and 50% (p = 0.0006), respectively, versus placebo. Both treatment groups also produced a statistically significant relative risk reduction in clinical vertebral fractures (49% and 48% for daily and intermittent ibandronate, respectively). Significant and progressive increases in lumbar spine (6.5%, 5.7%, and 1.3% for daily ibandronate, intermittent ibandronate, and placebo, respectively, at 3 years) and hip BMD, normalization of bone turnover, and significantly less height loss than in the placebo group were also observed for both ibandronate regimens. The overall population was at low risk for osteoporotic fractures. Consequently, the incidence of nonvertebral fractures was similar between the ibandronate and placebo groups after 3 years (9.1%, 8.9%, and 8.2% in the daily, intermittent, and placebo groups, respectively; difference between arms not significant). However, findings from a posthoc analysis showed that the daily regimen reduces the risk of nonvertebral fractures (69%; p = 0.012) in a higher-risk subgroup (femoral neck BMD T score < -3.0). In addition, oral ibandronate was well tolerated. Oral ibandronate, whether administered daily or intermittently with an extended between-dose interval of >2 months, is highly effective in reducing the incidence of osteoporotic fractures in postmenopausal women. This is the first time that significant fracture efficacy has been prospectively shown with an intermittently administered bisphosphonate in the overall study population of a randomized, controlled clinical trial. Thus, oral ibandronate holds promise as an effective and convenient alternative to current bisphosphonate therapies.

Change in bone turnover and hip, non-spine, and vertebral fracture in alendronate-treated women: the fracture intervention trial.

UNLABELLED: We used data from the Fracture Intervention Trial to assess the relationship change in bone turnover after 1 year of alendronate or placebo treatment and subsequent hip, non-spine, and spine fracture risk among 6186 postmenopausal women. In the alendronate group (n = 3105), greater reductions in one or more biochemical marker were associated with a lower risk of fracture. INTRODUCTION: There are few data on the relationship between short-term change in biochemical markers of bone turnover and non-spine fracture risk among bisphosphonate-treated women, and the clinical use of such measurements is unknown. MATERIALS AND METHODS: We measured biochemical markers of bone turnover (bone-specific alkaline phosphatase [bone ALP], intact N-terminal propeptide of type I collagen, and C-terminal crosslinked telopeptide of type 1 collagen) and BMD of the spine and hip at baseline and after 1 year of alendronate or placebo. During a mean follow-up of 3.6 years, 72 hip, 786 non-spine, and 336 vertebral fractures were documented. RESULTS AND CONCLUSIONS: Each 1 SD reduction in 1-year change in bone ALP was associated with fewer spine (odds ratio = 0.74; CI: 0.63, 0.87), non-spine (relative hazard [RH] = 0.89; CI: 0.78, 1.00; p < 0.050), and hip fractures (RH = 0.61; CI: 0.46, 0.78). Alendronate-treated women with at least a 30% reduction in bone ALP had a lower risk of non-spine (RH = 0.72; CI: 0.55, 0.92) and hip fractures (RH = 0.26; CI: 0.08, 0.83) relative to those with reductions <30%. We conclude that greater reductions in bone turnover with alendronate therapy are associated with fewer hip, non-spine, and vertebral fractures, and the effect is at least as strong as that observed with 1-year change in BMD.

Randomized trial of effect of alendronate continuation versus discontinuation in women with low BMD: results from the Fracture Intervention Trial long-term extension.

UNLABELLED: To determine the effects of continuation versus discontinuation of alendronate on BMD and markers of bone turnover, we conducted an extension trial in which 1099 older women who received alendronate in the FIT were re-randomized to alendronate or placebo. Compared with women who stopped alendronate, those continuing alendronate for 3 years maintained a higher BMD and greater reduction of bone turnover, showing benefit of continued treatment. However, among women who discontinued alendronate and took placebo in the extension, BMD remained higher, and reduction in bone turnover was greater than values at FIT baseline, showing persistence of alendronate's effects on bone. INTRODUCTION: Prior trials including the Fracture Intervention Trial (FIT) have found that therapy with alendronate increases BMD and decreases fracture risk for up to 4 years in postmenopausal women with low BMD. However, it is uncertain whether further therapy with alendronate results in preservation or further gains in BMD and if skeletal effects of alendronate continue after treatment is stopped. MATERIALS AND METHODS: We conducted a follow-up placebo-controlled extension trial to FIT (FIT long-term extension [FLEX]) in which 1099 women 60-86 years of age who were assigned to alendronate in FIT with an average duration of use of 5 years were re-randomized for an additional 5 years to alendronate or placebo. The results of a preplanned interim analysis at 3 years are reported herein. Participants were re-randomized to alendronate 10 mg/day (30%), alendronate 5 mg/day (30%), or placebo (40%). All participants were encouraged to take a calcium (500 mg/day) and vitamin D (250 IU/day) supplement. The primary outcome was change in total hip BMD. Secondary endpoints included change in lumbar spine BMD and change in markers of bone turnover (bone-specific alkaline phosphatase and urinary type I collagen cross-linked N-telopeptide). RESULTS: Among the women who had prior alendronate therapy in FIT, further therapy with alendronate (5 and 10 mg groups combined) for 3 years compared with placebo maintained BMD at the hip (2.0% difference; 95% CI, 1.6-2.5%) and further increased BMD at the spine (2.5% difference; 95% CI, 1.9-3. 1%). Markers of bone turnover increased among women discontinuing alendronate, whereas they remained stable in women continuing alendronate. Cumulative increases in BMD at the hip and spine and reductions in bone turnover from 8.6 years earlier at FIT baseline were greater for women continuing alendronate compared with those discontinuing alendronate. However, among women discontinuing alendronate and taking placebo in the extension, BMD remained higher and reduction in bone turnover was greater than values at FIT baseline. CONCLUSIONS: Compared with women who stopped alendronate after an average of 5 years, those continuing alendronate maintained a higher BMD and greater reduction of bone turnover, showing benefit of continued alendronate treatment on BMD and bone turnover. On discontinuation of alendronate therapy, rates of change in BMD at the hip and spine resumed at the background rate, but discontinuation did not result in either accelerated bone loss or a marked increase in bone turnover, showing persistence of alendronate's effects on bone. Data on the effect of continuation versus discontinuation on fracture risk are needed before making definitive recommendations regarding the optimal length of alendronate treatment.

Oral daily ibandronate prevents bone loss in early postmenopausal women without osteoporosis.

UNLABELLED: Oral daily ibandronate was investigated for the prevention of bone loss in postmenopausal women without osteoporosis (n = 653). BMD at the lumbar spine and hip were significantly increased (3.1% and 1.8%, respectively; p < or = 0.0001 versus placebo) with 2.5 mg ibandronate after 24 months. Oral ibandronate is a promising option for the prevention of postmenopausal bone loss. INTRODUCTION: Further strategies to manage patients most at risk from developing postmenopausal osteoporosis are required. The objectives of this multicenter, double-blind, randomized, placebo-controlled study were to examine the efficacy, tolerability, and optimal dose of oral daily ibandronate in the prevention of bone loss in postmenopausal women. MATERIALS AND METHODS: In total, 653 women (mean bone mineral density [BMD] T-score > -2.5 at the lumbar spine), who had been postmenopausal for at least 1 year, were allocated to one of four strata based on time since menopause and baseline lumbar spine BMD. Women were randomized to receive calcium (500 mg daily) plus either placebo (n = 162) or ibandronate 0.5 mg (n = 162), 1 mg (n = 166), or 2.5 mg (n = 163) as once-daily oral treatment for 2 years. The primary endpoint was the mean percent change in lumbar spine BMD with ibandronate versus placebo. RESULTS AND CONCLUSIONS: After 2 years, oral daily ibandronate produced a dose-related and sustained maintenance or increase in BMD at the lumbar spine and hip (total hip, femoral neck, trochanter), together with a dose-related reduction in the rate of bone turnover. The greatest nominal increases in spinal and hip BMD were observed with the 2.5-mg dose, which produced statistically significant BMD gains compared with placebo at 6 months and all subsequent time-points at the spine and hip (3.1% and 1.8% increase in lumbar spine and total hip BMD, respectively, versus placebo; p < or = 0.0001 after 24 months). Oral daily ibandronate was well tolerated with an incidence of upper gastrointestinal adverse events similar to placebo. No safety concerns were identified. In summary, oral daily ibandronate 2.5 mg decreases bone turnover, preserves or increases BMD in the spine and proximal femur, and is well tolerated. Oral ibandronate provides a promising option for the prevention of bone loss in postmenopausal women.

Genetic predisposition for adult lactose intolerance and relation to diet, bone density, and bone fractures.

UNLABELLED: Evidence that genetic disposition for adult lactose intolerance significantly affects calcium intake, bone density, and fractures in postmenopausal women is presented. PCR-based genotyping of lactase gene polymorphisms may complement diagnostic procedures to identify persons at risk for both lactose malabsorption and osteoporosis. INTRODUCTION: Lactase deficiency is a common autosomal recessive condition resulting in decreased intestinal lactose degradation. A -13910 T/C dimorphism (LCT) near the lactase phlorizin hydrolase gene, reported to be strongly associated with adult lactase nonpersistence, may have an impact on calcium supply, bone density, and osteoporotic fractures in the elderly. MATERIALS AND METHODS: We determined LCT genotypes TT, TC, and CC in 258 postmenopausal women using a polymerase chain reaction-based assay. Genotypes were related to milk intolerance, nutritional calcium intake, intestinal calcium absorption, bone mineral density (BMD), and nonvertebral fractures. RESULTS: Twenty-four percent of all women were found to have CC genotypes and genetic lactase deficiency. Age-adjusted BMD at the hip in CC genotypes and at the spine in CC and TC genotypes was reduced by -7% to -11% depending on the site measured (p = 0.04). LCT(T/C-13910) polymorphisms alone accounted for 2-4% of BMD in a multiple regression model. Bone fracture incidence was significantly associated with CC genotypes (p = 0.001). Milk calcium intake was significantly lower (-55%, p = 0.004) and aversion to milk consumption was significantly higher (+166%, p = 0.01) in women with the CC genotype, but there were no differences in overall dietary calcium intake or in intestinal calcium absorption test values. CONCLUSION: The LCT(T/C-13910) polymorphism is associated with subjective milk intolerance, reduced milk calcium intake, and reduced BMD at the hip and the lumbar spine and may predispose to bone fractures. Genetic testing for lactase deficiency may complement indirect methods in the detection of individuals at risk for both lactose malabsorption and osteoporosis.

Bone mineral density in fibromyalgia patients--correlation to disease activity.

OBJECTIVE: To compare bone mass (BMD) in women with fibromyalgia (FM) with healthy females, and to evaluate whether self-reported pain and lack of functional capacity correlate to reduced BMD in FM patients. METHODS: Thirty-one FM patients (20 pre- and 11 postmenopausal) and fourty-one healthy women (30 pre- and 10 postmenopausal) were enrolled in the study. BMD of the lumbar spine and the femoral neck was measured by a DEXA (Norland) scanner. Self reported pain was measured on a Visual Analog Scale (VAS). The Activity of Daily Living (ADL) component of the Fibromyalgia Impact Questionnaire (FIQ-ADL) was used as measure for physical capacity. RESULTS: BMD-lumbar spine and BMD-femoral neck did not differ significantly between FM patients and controls, though premenopausal FM patients tended to have lower BMD-femoral neck (p = 0.09). Self reported pain and FIQ-ADL among FM patients correlated with BMD-femoral neck (r(s) = -0.52, p = 0.003); (r(s) = -0.31, p = 0.09). CONCLUSION: Premenopausal FM patients tended to have lower BMD of hip than controls. Self reported pain correlated negatively to BMD. Thus, the severity of FM might have a negative impact on bone mass.

Relationship between leptin levels and bone mineral density in the elderly.

OBJECTIVE: To assess the relationship between circulating leptin levels, bone mineral content and density in the elderly. DESIGN: A cross-sectional study. PATIENTS: A cohort of 92 men and 171 women, with ages ranging from 68 to 75 years, selected as a healthy and normal functioning group, in the city centre of Verona. MEASUREMENTS: Plasma leptin levels were determined in each participant. Body composition was evaluated with dual energy X-ray absorptiometry (DXA). Bone mineral content (BMC) and bone mineral density (BMD) were measured at whole-body, hip and femoral neck level in all subjects. RESULTS: In both men and women a significant relationship between fat mass and whole-body BMC or BMD was found. The strength of this association was consistently reduced after adjustment for plasma leptin. A significant association between circulating leptin levels, whole-body, total hip and femoral neck BMC and BMD was found in both sexes. This association retained the statistical significance after adjustment for fat mass percentage, especially in women. In stepwise multiple linear regression analyses, leptin was shown to be a significant predictor of whole-body, total hip and femoral neck BMC and BMD, independently of age and the percentage of body fat in both sexes. The circulating levels of leptin accounted for a variance in whole-body BMC of 8.9% in men and 18.2% in women, and in whole-body BMD of 10.6% in women. CONCLUSION: Our data show a significant relationship between leptin, bone mineral mass and density in healthy elderly men and women.