Fracture Rate, Quality of Life and Back Pain in Patients with Osteoporosis Treated with Teriparatide: 24-Month Results from the Extended Forsteo Observational Study (ExFOS).

We describe the pre-planned interim analysis of fracture outcomes, health-related quality of life (HRQoL) and back pain in patients with severe osteoporosis treated with teriparatide for up to 24 months in the Extended Forsteo (Forsteo(®) is a registered trade name of Eli Lilly and Company) Observational Study (ExFOS), a prospective, multinational, observational study. Data on incident clinical fractures, HRQoL (EQ-5D questionnaire) and back pain [100 mm visual analogue scale (VAS)] were collected. The number of patients with fractures was summarised in 6-month intervals and fracture rate over each 6-month period was assessed using logistic regression for repeated measures. Changes from baseline in EQ-5D and back pain VAS were analysed using mixed models for repeated measures. Of 1454 patients in the active treatment cohort, 90.6 % were female and 14.4 % were taking glucocorticoids. During teriparatide treatment (median duration 23.7 months), 103 patients (7.1 %) sustained a total of 122 incident clinical fractures (21 % vertebral, 79 % non-vertebral). A 49 % decrease in the odds of fractures and a 75 % decrease in the odds of clinical vertebral fractures were observed in the >18- to 24-month period versus the first 6-month period (both p < 0.05). EQ-5D scores and back pain VAS scores were significantly improved from baseline at each post-baseline observation during teriparatide treatment. In conclusion, patients with severe osteoporosis showed a significant reduction in the incident fracture rate during 24 months of teriparatide treatment in routine clinical practice, accompanied by a significant improvement in HRQoL and reduction in back pain. Results should be interpreted in the context of the non-controlled design of this observational study.

A novel monthly dosing regimen of risedronate for the treatment of postmenopausal osteoporosis: 2-year data.

This 2-year trial evaluated the efficacy and tolerability of a monthly oral regimen of risedronate. Postmenopausal women with osteoporosis were randomly assigned to double-blind treatment with risedronate 75 mg on 2 consecutive days each month (2CDM) or 5 mg daily. The primary end point was the percentage change from baseline in lumbar spine bone mineral density (BMD) at 12 months. Secondary end points included the change in BMD of the lumbar spine and proximal femur and in bone turnover markers as well as the number of subjects with at least one new vertebral fracture over 24 months. Among 1,229 patients who were randomized and received at least one dose of risedronate, lumbar spine BMD was increased in both treatment groups: mean percentage change from baseline was 4.2 ± 0.19 and 4.3 ± 0.19 % in the 75 mg 2CDM and 5 mg daily groups, respectively, at month 24. The treatment difference was 0.17 (95 % confidence interval -0.35 to 0.68). There were no statistically significant differences between treatment groups on any secondary efficacy parameters. Both treatment regimens were well tolerated. Risedronate 75 mg 2CDM was noninferior in BMD efficacy and did not show a difference in tolerability compared to 5 mg daily after 24 months of treatment in women with postmenopausal osteoporosis. This monthly regimen may provide a more convenient dosing schedule to some patients with postmenopausal osteoporosis.

Chronic and intermittent exposure to alcohol vapors: a new model of alcohol-induced osteopenia in the rat.

BACKGROUND: Different models are used to study the effects of chronic alcohol consumption on bone tissue in the rat. However, the current models take several months to show indices of osteopenia as observed in chronic drinkers. Numerous studies have supported that chronic and intermittent exposure to ethanol vapors has predictive validity as a model of alcohol dependence in humans. However, this model has never been applied to bone research to study its effects on the parameters that define osteopenia. This was the goal of this study in the rat. METHODS: Male Wistar rats were exposed to ethanol vapor inhalation (n = 6) or air (controls, n = 6). Animals were exposed to chronic (11 weeks) and intermittent (14 hours a day) ethanol vapor reaching stable blood alcohol levels (BALs; 150 to 250 mg/dl) at the end of the third week of inhalation. After the sacrifice, right and left femur and tibia were dissected free of fat and connective tissue and bone mineral density (BMD) was assessed by dual X-ray absorptiometry. The microarchitecture of the femur was studied using microcomputed tomography. RESULTS: The BMD of the left and right femurs and the left tibia was lower in the ethanol group compared with the control group. The bone volume fraction (BV/TV) and the bone surface density (BS/TV) were lower in the ethanol group compared with control animals. The trabecular number (Tb.N) was lower in the ethanol group while the trabecular spacing was higher. CONCLUSIONS: The decrease in the BMD, BV/TV, and Tb.N is in the same range as what is observed in human drinkers and what is reported with other animal alcohol models (Lieber-DeCarli liquid diet, ethanol in the tap water). Therefore, this model could be useful to study the effects of chronic alcohol consumption in the bone research field and has the advantage of controlling easily targeted BALs.

Bone mineral density, hip bone geometry, and calcaneus trabecular bone texture in obese and normal-weight children.

Our study aimed at comparing bone mineral density (BMD), geometric indices of hip bone strength, and indices of trabecular bone texture at the calcaneus in obese and normal-weight children. Fifty-three obese children (10.3 ± 1.4 yr) and 24 normal-weight children (10.4 ± 1.5 yr) participated in this study. Body composition, bone mineral content, and BMD at whole body (WB), lumbar spine (L2-L4), total forearm, and proximal femur (total hip [TH] and femoral neck [FN]) were measured by dual-energy X-ray absorptiometry (DXA). Bone geometry of the hip was evaluated by the hip structure analysis (HSA) program. DXA scans were analyzed at the FN at its narrowest region and the femoral shaft (FS) by the HSA program. Cross-sectional area (CSA) and section modulus (Z) were measured from hip BMD profiles. Texture analysis was performed on digitized radiographs of the calcaneus to assess trabecular bone microarchitecture, and the result was expressed as Hmean. WB BMD, L2-L4 BMD, TH BMD, and FN BMD were significantly higher in obese children compared with normal-weight peers (p < 0.05). FN Z and FS Z were not significantly different between the 2 groups, whereas Hmean parameter was significantly lower in obese children compared with normal-weight peers (p < 0.001). After adjustment for body weight, obese children displayed lower WB BMD, FN CSA, FN Z, FS CSA, and FS Z compared with normal-weight children. This study suggests that BMD of WB and geometric indices of hip bone strength are not adapted to the increased body weight in obese children.

Morphea-like skin reactions in patients treated with the cathepsin K inhibitor balicatib.

BACKGROUND: In a multicenter clinical trial in North America and Europe that tested the cathepsin K (catK) inhibitor balicatib for the treatment of osteoporosis, several patients developed hardening of the skin. OBJECTIVE: We sought to characterize these observed adverse events. METHODS: Patients with skin hardening were examined by a local dermatologist. All of those patients except one had at least one biopsy specimen taken from affected skin, which was read by local and two central dermatopathologists. Workup was directed for consideration of systemic scleroderma. RESULTS: Nine patients of 709 treated with balicatib developed skin hardening and were given a diagnosis of morphea-like skin changes. No such events were observed in patients taking placebo or the lowest balicatib dose. After discontinuation of balicatib, skin changes resolved completely in 8 and partially in one patient. LIMITATIONS: Each patient was seen by a different dermatologist in 6 different countries. CONCLUSIONS: These observations are likely dose-related adverse effects of balicatib. Although catK was originally thought to be expressed only in osteoclasts, it has more recently also been found in lung and dermal fibroblasts and been implicated in the degradation of the extracellular matrix in the lung and the skin. It is therefore plausible that the observed dermal fibrosis in balicatib-treated patients is a result of impaired degradation of extracellular matrix proteins and may represent a class effect of catK inhibitors. We recommend that further exploration of catK inhibition for the treatment of osteoporosis or cancer should include monitoring for similar adverse effects.

Osteocyte apoptosis and lipid infiltration as mechanisms of alcohol-induced bone loss.

AIMS: We carried out an in vivo study to assess the relationship between increase in adiposity in the marrow and osteocyte apoptosis in the case of alcohol-induced bone loss. METHODS AND RESULTS: After alcohol treatment, the number of apoptotic osteocytes was increased and lipid droplets were accumulated within the osteocytes, the bone marrow and the cortical bone micro-vessels. At last, we found an inverse correlation between bone mineral density and osteocyte apoptosis and strong significant correlations between the osteocyte apoptotic number and lipid droplet accumulation in osteocyte and bone micro-vessels. CONCLUSION: These data show that alcohol-induced bone loss is associated with osteocyte apoptosis and lipid accumulation in the bone tissue. This lipid intoxication, or 'bone steatosis', is correlated with lipid accumulation in bone marrow and blood micro-vessels.

Hip cortical thickness assessment in postmenopausal women with osteoporosis and strontium ranelate effect on hip geometry.

The aims of this study were to assess the relationship between hip geometry and the 5-yr risk of hip fractures in postmenopausal osteoporotic women and the effects of strontium ranelate on these parameters. Using the 5-yr data of a randomized placebo-controlled trial of strontium ranelate (Treatment of Peripheral Osteoporosis Study [TROPOS]), we reanalyzed the hip dual-energy X-ray absorptiometry scans to determine the role of hip geometry in the risk of hip fractures (placebo group, n=636) and to analyze the effects of strontium ranelate (n=483). The outcomes included the hip structure analysis (HSA) parameters: cross-sectional area (CSA), section modulus, cortical thickness, and buckling ratio, measured at femoral neck, intertrochanteric (IT) region, and proximal shaft. The geometric parameters associated with an increased risk of hip fracture over 5yr were IT CSA and femoral shaft cortical thickness independent of age and total-hip bone mineral density (BMD). Using Bonferroni adjustment, IT cortical thickness was associated with the risk of hip fracture. Over 5yr, significant decreases in some femoral dimensions of the placebo group contrast with significant increases in strontium ranelate group after adjustment for age and BMD. Using Bonferroni adjustment, differences between placebo and strontium ranelate groups were no longer significant after adjustment on 5-yr BMD changes. Some HSA parameters have predictive value for hip fracture risk in postmenopausal osteoporotic women. Strontium ranelate improves some HSA parameters, through the BMD increase.

Osteocalcin-insulin relationship in obese children: a role for the skeleton in energy metabolism.

OBJECTIVE: Osteocalcin is a bone-specific protein secreted by osteoblasts and often used as a bone formation biomarker. Rodent studies have reported a hormonal role of osteocalcin on glucose metabolism, increasing insulin secretion and sensitivity and increasing energy expenditure. However, it is unknown whether osteocalcin fulfils the same function in humans. METHODS: We investigated the relationship between serum osteocalcin and insulin concentrations in 27 prepubertal obese children (9-12 years old) randomly divided into two groups, one of which entered a physical training programme, and 16 nonobese control children. Whole body bone mineral density (WB-BMD), serum osteocalcin, circulating insulin and adiponectin were measured at baseline and after 6 months. RESULTS: Trained and untrained obese children had higher WB-BMD than controls at baseline. Trained children also displayed a significant insulin increase and a significant adiponectin decrease while osteocalcin was increased compared to untrained obese children. Significant linear correlations between WB-BMD and adiponectin, delta BMD (variation between baseline and after-training values) and delta adiponectin, insulin and osteocalcin, delta insulin and delta osteocalcin, delta insulin and delta under-carboxylated osteocalcin were found only in trained obese children with no significant relationship in control and untrained obese children. CONCLUSIONS: In trained obese children, correlations indicate that when BMD is increased, osteocalcin is increased and insulin lowered. This suggests that increased BMD is associated with increased energy metabolism and a decreased level of insulin. We thus report statistically significant relationships between the skeleton (osteocalcin) and energy metabolism (insulin), suggesting a regulatory hormonal loop including osteocalcin and insulin.

Positive influence of long-lasting and intensive weight-bearing physical activity on hip structure of young adults.

The aim was to analyze the associations between high-intensity and long-lasting weight-bearing sports with hip structure in young adults. One hundred and seventy-two subjects aged 17-28 yr were divided into 4 groups: 40 athlete women (10.2 ± 2.2 h/wk), 30 control women, 67 athlete men (11.4 ± 3.6 h/wk), and 35 control men. The nondominant femur, lumbar spine, and whole body were scanned by dual-energy X-ray absorptiometry to assess bone mineral content (BMC) and bone mineral density (BMD). Hip structure analysis (HSA) software was applied to evaluate cross-sectional area, cross-sectional moment of inertia, and section modulus at the femoral neck, intertrochanter, and femoral shaft regions. All the BMC and BMD values were significantly higher in athletes of both sexes compared with controls (p < 0.05). Most of the hip structural parameters were significantly higher (p < 0.05) in athletes compared with controls. Most of the differences were maintained after adjustments for height, weight, and calcium intake. Positively significant correlations were observed between HSA parameters and physical activity variables in both sexes (r > 0.32; p < 0.05). Partial correlation suggested that the hours of practice appeared to have a greater influence than the years of practice on hip bone geometry. These results suggest that external mechanical loading is a strong determinant of hip bone structure when weight-bearing physical activity is commenced before puberty and maintained during adulthood.

Combined effects of chronic alcohol consumption and physical activity on bone health: study in a rat model.

Chronic alcohol consumption may be deleterious for bone tissue depending on the amount of ethanol consumed, whereas physical activity has positive effects on bone. This study was designed to analyze the effects of moderate alcohol consumption on bone in trained rats. 48 male Wistar rats were divided into four groups: control (C), alcohol (A), exercise (E) and alcohol + exercise (AE). A and AE groups drank a solution composed of water and ethanol. E and AE groups were trained for 2 months (treadmill: 40 min/day, 5 times/week). Body composition and bone mineral density (BMD) were assessed by dual X-ray absorptiometry and microarchitectural parameters using micro-computed tomography. Serum osteocalcin and CTx were determined by ELISA assays. The body weight and lean mass gain were lower in group A, while the fat mass gain was lower in exercised groups. BMD and BMC were higher with alcohol after body weight adjustment. Trabecular thickness was significantly higher in AE and A groups compared to C and E; cross-sectional area was larger in A and C groups compared to AE and E. CTx levels were higher in A compared to C and in AE and E versus C and A. Osteocalcin levels were significantly greater in AE and E groups versus C and A. In conclusion, the light to moderate alcohol consumption over a short period increased the trabecular thickness, BMC and BMD in A and AE groups. However, we observed alterations in bone remodeling and body composition with alcohol, at the end of the protocol, which did not appear when alcohol was combined to exercise.

Local plate/rod descriptors of 3D trabecular bone micro-CT images from medial axis topologic analysis.

PURPOSE: Trabecular bone microarchitecture is made of a complex network of plate and rod structures evolving with age and disease. The purpose of this article is to propose a new 3D local analysis method for the quantitative assessment of parameters related to the geometry of trabecular bone microarchitecture. METHODS: The method is based on the topologic classification of the medial axis of the 3D image into branches, rods, and plates. Thanks to the reversibility of the medial axis, the classification is next extended to the whole 3D image. Finally, the percentages of rods and plates as well as their mean thicknesses are calculated. The method was applied both to simulated test images and 3D micro-CT images of human trabecular bone. RESULTS: The classification of simulated phantoms made of plates and rods shows that the maximum error in the quantitative percentages of plate and rods is less than 6% and smaller than with the structure model index (SMI). Micro-CT images of human femoral bone taken in osteoporosis and early or advanced osteoarthritis were analyzed. Despite the large physiological variability, the present method avoids the underestimation of rods observed with other local methods. The relative percentages of rods and plates were not significantly different between osteoarthritis and osteoporotic groups, whereas their absolute percentages were in relation to an increase of rod and plate thicknesses in advanced osteoarthritis with also higher relative and absolute number of nodes. CONCLUSIONS: The proposed method is model-independent, robust to surface irregularities, and enables geometrical characterization of not only skeletal structures but entire 3D images. Its application provided more accurate results than the standard SMI on simple simulated phantoms, but the discrepancy observed on the advanced osteoarthritis group raises questions that will require further investigations. The systematic use of such a local method in the characterization of trabecular bone samples could provide new insight in bone microarchitecture changes related to bone diseases or to those induced by drugs or therapy.

[Body mass index and quantitative osseous ultrasonography of the phalanges in Lebanese post-menarcheal adolescent girls]. / Indice de masse corporelle et ultrasonographie quantitative osseuse des phalanges chez des adolescentes libanaises réglées.

AIM OF THE STUDY: To explore the relation between body mass index and phalanx ultrasound measurements in a group of Lebanese post-menarchal girls. METHODS AND RESULTS: Amplitude-dependent speed of sound (AD-SoS) and bone transmission time (BTT) were measured in 168 post-menarchal girls aged 12-17 years using a DBM sonic bone profiler device. Anthropometrical characteristics (weight and height) were measured. Age and maturation index (years since menarche) were positively related to AD-SoS and BTT (p < 0.01). AD-SoS values were negatively related to BMI and body weight (r = -0,27; p < 0.001 and r = - 0,25; p < 0.001 respectively). There was no relation between BTT values and neither BMI nor body weight. Overweight girls (n = 36) had lower AD-SoS values than normal-weight girls (n = 122) (1994 +/- 87 m x sec(-1) vs 2041 +/- 82 m x sec(-1) respectively; p < 0.01). Obese girls (n = 10) had lower AD-SoS values than normal-weight girls (n = 122) (1976 +/- 96 m x sec(-1) vs 2041 +/- 82 m x sec(-1) respectively; p < 0.05). CONCLUSION: In this group of Lebanese post-menarchal girls, AD-SoS values are inversely correlated to BMI while BTT values were not related to BMI.

Oxytocin controls differentiation of human mesenchymal stem cells and reverses osteoporosis.

Osteoporosis constitutes a major worldwide public health burden characterized by enhanced skeletal fragility. Bone metabolism is the combination of bone resorption by osteoclasts and bone formation by osteoblasts. Whereas increase in bone resorption is considered as the main contributor of bone loss that may lead to osteoporosis, this loss is accompanied by increased bone marrow adiposity. Osteoblasts and adipocytes share the same precursor cell and an inverse relationship exists between the two lineages. Therefore, identifying signaling pathways that stimulate mesenchymal stem cells osteogenesis at the expense of adipogenesis is of major importance for developing new therapeutic treatments. For this purpose, we identified by transcriptomic analysis the oxytocin receptor pathway as a potential regulator of the osteoblast/adipocyte balance of human multipotent adipose-derived stem (hMADS) cells. Both oxytocin (OT) and carbetocin (a stable OT analogue) negatively modulate adipogenesis while promoting osteogenesis in both hMADS cells and human bone marrow mesenchymal stromal cells. Consistent with these observations, ovariectomized (OVX) mice and rats, which become osteoporotic and exhibit disequilibrium of this balance, have significant decreased OT levels compared to sham-operated controls. Subcutaneous OT injection reverses bone loss in OVX mice and reduces marrow adiposity. Clinically, plasma OT levels are significantly lower in postmenopausal women developing osteoporosis than in their healthy counterparts. Taken together, these results suggest that plasma OT levels represent a novel diagnostic marker for osteoporosis and that OT administration holds promise as a potential therapy for this disease.

Total body, lumbar spine and hip bone mineral density in overweight adolescent girls: decreased or increased?

Despite the epidemic of overweight adolescents, the effect of being overweight on bone mineral density (BMD) during this period is poorly understood. However, recent studies have suggested that overweight adolescents have lower BMD compared to normal-weighted adolescents after adjusting for body weight. The aim of this study was to determine the influence of being overweight on bone status in a group of adolescent girls. This study included 22 overweight (BMI >25 kg/m(2)) adolescent girls (15.4 +/- 2.4 years old) and 20 maturation-matched (15.2 +/- 1.9 years old) controls (BMI <25 kg/m(2)). Bone mineral area, bone mineral content, BMD at the whole body (WB), lumbar spine (L2-L4), femoral neck (FN), total hip (TH) and body composition (lean mass and fat mass) were assessed by dual-energy X-ray absorptiometry (DXA). Calculation of the bone mineral apparent density (BMAD) was completed for the WB and for L2-L4. Expressed as crude values, DXA measurements of BMD at all bone sites (TB, L2-L4, TH and FN) were higher in overweight adolescent girls compared to controls. After adjusting for either body weight, lean mass or fat mass, these differences disappeared. Finally, BMAD of the L2-L4 remained higher in overweight girls compared to controls after adjusting for lean mass. We conclude that overweight adolescent girls do not have lower BMD when compared with controls, even when BMD values are adjusted for weight, lean mass or fat mass.

Dual-energy X-ray absorptiometry assessment of tibial mid-third bone mineral density in young athletes.

We suggested a new reproducible method to measure densitometric values at mid-third part of the tibia by dual-energy X-ray absorptiometry (DXA; Delphi, Hologic, Waltham, MA) in a population of young adults. Our population was composed of 170 subjects aged 22.7+/-4.0 yr: athlete men (n=67) and women (n=40); control men (n=33) and women (n=30). Athletes practiced collective sports, judo or weightlifting for 10.0+/-3.6 h/wk. We measured bone area (cm2), bone mineral content (BMC, g), and bone mineral density (BMD, g/cm2) at the left total hip and the mid-third part of the tibia with DXA. For the tibia scan, we used the whole body mode. To ensure the reproducibility of the method, both legs were extended and the feet were maintained on a support in an internal rotation of 35 degrees. The region of interest of the lumbar spine from the whole body scan was positioned around the mid-third part of the tibia. Area, BMC, and BMD values were significantly higher in athletes compared with those of controls. The intra- and interobserver variability of the image analysis were 0.38% and 1.01%, respectively. For BMD measurements, the short-term (4 scans/d) and mid-term (4 scans/mo) reproducibility were 1.33% and 1.94%, respectively. DXA is a suitable tool to evaluate densitometric measurements at the mid-third part of the tibia and the influence of physical activity on that bone site.

Relative importance of lean and fat mass on bone mineral density in a group of adolescent girls and boys.

The aim of this study was to determine the relative importance of lean mass (LM) and fat mass (FM) on bone mineral density (BMD) in a group of adolescent girls and boys. A total of 65 adolescent boys and 35 adolescent girls participated in this study. Whole body (WB) and lumbar spine (L1-L4) BMD were measured by dual-energy X-ray absorptiometry (DXA). Body composition was assessed using the same technique. In boys, LM was strongly related to WBBMD (r = 0.68; p < 0.001) and to L1-L4 BMD (r = 0.61; p < 0.001), whereas FM was not positively related to BMD and was negatively associated with WB bone mineral apparent density (WBBMAD). In girls, both LM and FM were positively related to WBBMD (r = 0.41; p < 0.05 and r = 0.49; p < 0.01, respectively), whereas only FM was correlated to L1-L4 BMD (r = 0.33; p < 0.05). Finally, in a multiple regression analysis, FM was found to be a better positive determinant of WBBMD than LM in girls, whereas in boys, FM was found to be a negative determinant of WBBMD and L1-L4 BMD. This study suggests that LM is a strong determinant of WBBMD and L1-L4 BMD in boys, and that FM is a stronger determinant of WBBMD than LM in girls.

[Daily calcium intake and body mass index in a group of Lebanese adolescents]. / Apport calcique journalier et indice de masse corporelle chez des adolescents libanais.

AIM OF THE STUDY: To investigate the relationship between daily calcium intake (DCI) and body mass index (BMI) in a group of Lebanese adolescents. METHODS AND RESULTS: 419 adolescents (219 boys and 169 girls) aged 13-18 years participated in our study. DCI was calculated using a validated questionnaire, and anthropometrical characteristics (weight and height) were measured. In this study, only 20% of the adolescents met the adequate DCI recommendation of 1300 mg/day. Boys had a significantly higher mean DCI than girls (1023 +/- 360 mg/d and 839 +/- 303 mg/d respectively for boys and girls ; p < 0.001). DCI was negatively related to BMI in boys (r = -0,15; p < 0.05) but not in girls. Obese boys had a significantly lower mean DCI than those whose BMI was normal (869 +/- 249 mg/d and 1043 +/- 373 mg/d respectively ; p < 0.05). CONCLUSION: In this study, 80% of the adolescents do not meet the DCI adequate intake. It seems important to encourage these adolescents to increase their DCI. Moreover, this study shows that DCI is inversely related to age in girls and to BMI in boys.

Efficacy and safety of risedronate 150 mg once a month in the treatment of postmenopausal osteoporosis.

INTRODUCTION: Risedronate has been shown to be effective in the treatment of postmenopausal osteoporosis when given orally in daily or weekly doses or on 2 consecutive days per month. This randomized, double-blind, multi-center study was designed to assess the efficacy and safety of a single 150 mg risedronate once-a-month oral dose compared with the 5 mg daily regimen. METHODS: Women with postmenopausal osteoporosis were randomly assigned to receive risedronate 5 mg daily (n=642) or 150 mg once a month (followed by daily placebo) (n=650) in a double-blind fashion for 2 years. Study drug was taken on an empty stomach at least 30 min before breakfast. Bone mineral density, bone turnover markers, fractures, and adverse events were evaluated. The primary efficacy endpoint was the mean percent change from baseline in lumbar spine bone mineral density after 1 year. RESULTS: 538 patients in the daily group (83.8%) and 556 patients in the once-a-month group (85.5%) completed 1 year. The mean percent change in lumbar spine bone mineral density was 3.4% (95% confidence interval, 3.03% to 3.82%) in the daily group and 3.5% (95% confidence interval, 3.15% to 3.93%) in the once-a-month group. The difference between groups was -0.1% (95% confidence interval, -0.51% to 0.27%). The once-a-month regimen was determined to be non-inferior to the daily regimen based on prospectively defined criteria. The mean percent changes in bone mineral density at sites in the hip (total proximal femur, femoral neck, femoral trochanter) were also similar in both dose groups, as were the changes in biochemical markers of bone turnover. The incidence of adverse events, adverse events leading to withdrawal, and upper gastrointestinal tract adverse events were similar in the 2 treatment groups. Both regimens were well tolerated; the percent of patients who withdrew from treatment as a result of an adverse event was 9.5% in the daily group and 8.6% in the once-a-month group. CONCLUSIONS: Risedronate 150 mg once a month is similar in efficacy and safety to daily dosing and may provide an alternative for patients who prefer once-a-month oral dosing.

Combined effects of exercise and propranolol on bone tissue in ovariectomized rats.

UNLABELLED: The bone response to physical exercise may be under control of the SNS. Using a running session in rats, we confirmed that exercise improved trabecular and cortical properties. SNS blockade by propranolol did not affect this response on cortical bone but surprisingly inhibited the trabecular response. This suggests that the SNS is involved in the trabecular response to exercise but not in the cortical response. INTRODUCTION: Animal studies have suggested that bone remodeling is under beta-adrenergic control through the sympathetic nervous system (SNS). However, the SNS contribution to bone response under mechanical loading remains unclear. The purpose of this study was to examine the preventive effect of exercise coupled with propranolol on cancellous and cortical bone compartments in ovariectomized rats. MATERIALS AND METHODS: Six-month-old female Wistar rats were ovariectomized (OVX, n = 44) or sham-operated (n = 24). OVX rats received subcutaneous injections of propranolol 0.1 mg/kg/day or vehicle and were submitted or not submitted to treadmill exercise (13 m/minute, 60 minutes/day, 5 days/week) for 10 weeks. Tibial and femoral BMD was analyzed longitudinally by DXA. At death, the left tibial metaphysis and L(4) vertebrae were removed, and microCT was performed to study trabecular and cortical bone structure. Histomorphometric analysis was performed on the right proximal tibia. RESULTS: After 10 weeks, BMD and trabecular strength decreased in OVX rats, whereas bone turnover rate and cortical porosity increased compared with the Sham group (p < 0.001). Either propranolol or exercise allowed preservation of bone architecture by increasing trabecular number (+50.35% versus OVX; p < 0.001) and thickness (+16.8% versus OVX; p < 0.001). An additive effect of propranolol and exercise was observed on cortical porosity but not on trabecular microarchitecture or cortical width. Biomechanical properties indicated a higher ultimate force in the OVX-propranolol-exercise group compared with the OVX group (+9.9%; p < 0.05), whereas propranolol and exercise alone did not have any significant effect on bone strength. CONCLUSIONS: Our data confirm a contribution of the SNS to the determinants of bone mass and quality and show a antagonistic effect of exercise and a beta-antagonist on trabecular bone structure.

Estimation of the 3D self-similarity parameter of trabecular bone from its 2D projection.

It has been shown that the analysis of two dimensional (2D) bone X-ray images based on the fractional Brownian motion (fBm) model is a good indicator for quantifying alterations in the three dimensional (3D) bone micro-architecture. However, this 2D measurement is not a direct assessment of the 3D bone properties. In this paper, we first show that S(3D), the self-similarity parameter of 3D fBm, is linked to S(2D), that of its 2D projection, by S(3D)=S(2D)-0.5. In the light of this theoretical result, we have experimentally examined whether this relation holds for trabecular bone. Twenty one specimens of trabecular bone were derived from frozen human femoral heads. They were digitized using a high resolution mu-CT. Their projections were simulated numerically by summing the data in the three orthogonal directions and both 3D and 2D self-similarity parameters were measured. Results show that the self-similarity of the 3D bone volumes and that of their projections are linked by the previous equation. This demonstrates that a simple projection provides 3D information about the bone structure. This information can be a valuable adjunct to the bone mineral density for the early diagnosis of osteoporosis.