Oestrogen deficiency increases the rate of bone remodelling which, in association with a negative remodelling balance (resorption exceeding formation), results in impaired bone architecture, mass and ...strength. Current anti-osteoporotic drugs act on bone remodelling by inhibiting bone resorption or by promoting its formation. An alternative therapeutic approach is based on the concept of inducing opposite effects on bone resorption and formation. One therapeutic agent, strontium ranelate, was shown to induce opposite effects on bone resorption and formation in pre-clinical studies and to reduce fracture risk in postmenopausal osteoporotic patients. How strontium ranelate acts to improve bone strength in humans remains a matter of debate, however. This review of the most recent pre-clinical and clinical studies is a critical analysis of strontium ranelate’s action on bone resorption and formation and how it increases bone mass, microarchitecture and strength in postmenopausal osteoporotic women.
In Germany, accurate data on the prevalence and treatment of osteoporosis, as well as the cost of this illness, are not available. The aim of this study is to give a valid estimation of these items ...for the year 2003.
Routine data from a German sickness fund covering 1.5 million beneficiaries and billing data for outpatient visits were used to obtain estimates of prevalence for osteoporosis. Claims data for patients with osteoporosis (M80, M81) or an osteoporosis-related fracture diagnosis (S22, S32, S42, S52, S72, S82) or treatment with anti-osteoporosis drugs were examined. Costs were calculated from the perspective of the German health insurance system and the German nursing care insurance system, respectively. Only direct costs of osteoporosis were considered.
In 2003, 7.8 million Germans (6.5 million women) were affected by osteoporosis. Of them, 4.3% experienced at least one clinical fracture. Only 21.7% were treated with an anti-osteoporosis drug. The total direct costs attributable to osteoporosis amounted to euros 5.4 billion.
This study confirms that osteoporosis is underdiagnosed, undertreated and imposes a considerable economic burden on the health system in Germany. Effective strategies for the prevention and management of this disease are needed.
Abstract Earlier studies found the recovery of bone loss after clinical immobilization to be incomplete. It has been argued that this is due to the human skeleton's inability to accrue bone mass once ...peak bone mass has been attained. However, recent studies suggest that bone losses can fully recover when complete functional rehabilitation is achieved. Accordingly, we hypothesized that bone losses by experimental bed rest would recover within one-year of follow-up. Twenty-five men (mean age 32 years, SD 4.2) were randomly assigned to either bed rest only (Ctrl), resistive flywheel exercise (FW), or to a group receiving 60 mg. i.v pamidronate prior to bed rest (Pam). Calf muscle cross sectional area and bone mineral content of the tibia was measured by peripheral quantitative computed tomography. Calcium, PTH and alkaline phosphatase blood levels were assessed along with urinary desoxypyridinoline excretion. Physical activity was assessed by the Freiburg questionnaire. In Pam and FW, diaphyseal bone losses were completely recovered at a 180-day follow-up, and there was even a small surplus after 1 year ( p = 0.016). Epiphyseal bone losses were largely, although not completely recovered after 1 year, when they still amounted to − 0.6% (SD 1.3%, p = 0.034, averaged over all groups). Bone formation and resorption markers had returned to baseline values at this time. However, epiphyseal recovery may still have been on-going, and fitting an exponential model yielded full recovery of the epiphysis within 2 years. Importantly, recovery of calf muscle cross-section and resumption of impact sport activities seemed to precede bone recovery, and bone accrual was closely matching the prior losses on an individual basis. No relationship was found between the epiphyseal BMC deficit at one-year follow-up and the participants' age. Results demonstrate recovery of bed rest induced bone losses in healthy adults. The initial re-accrual rate was remarkably high and is comparable to the accrual of bone mass during the pubertal growth spurt. This and the fact that the recovery of bone appeared to be tightly regulated, and generally followed neuromuscular recovery underline the adult skeleton's capability to adapt to mechanical stimuli.
Background: Strontium ranelate, a new oral drug shown to reduce vertebral fracture risk in postmenopausal women with osteoporosis, was studied in the Treatment of Peripheral Osteoporosis (TROPOS) ...study to assess its efficacy and safety in preventing nonvertebral fractures also.
Methods: Strontium ranelate (2 g/d) or placebo were randomly allocated to 5091 postmenopausal women with osteoporosis in a double-blind placebo-controlled 5-yr study with a main statistical analysis over 3 yr of treatment.
Findings: In the entire sample, relative risk (RR) was reduced by 16% for all nonvertebral fractures (P = 0.04), and by 19% for major fragility fractures (hip, wrist, pelvis and sacrum, ribs and sternum, clavicle, humerus) (P = 0.031) in strontium ranelate-treated patients in comparison with the placebo group. Among women at high risk of hip fracture (age ≥74 yr and femoral neck bone mineral density T score ≤−3, corresponding to −2.4 according to NHANES reference) (n = 1977), the RR reduction for hip fracture was 36% (P = 0.046). RR of vertebral fractures was reduced by 39% (P < 0.001) in the 3640 patients with spinal x-rays and by 45% in the subgroup without prevalent vertebral fracture.
Strontium ranelate increased bone mineral density throughout the study, reaching at 3 yr (P < 0.001): +8.2% (femoral neck) and +9.8% (total hip).
Incidence of adverse events (AEs) was similar in both groups.
Conclusion: This study shows that strontium ranelate significantly reduces the risk of all nonvertebral and in a high-risk subgroup, hip fractures over a 3-yr period, and is well tolerated. It confirms that strontium ranelate reduces vertebral fractures. Strontium ranelate offers a safe and effective means of reducing the risk of fracture associated with osteoporosis.
Summary
Older women with low bone mass are at higher risk of fracture and there is limited data on what is associated with risk of falls. We found explosive jumping to relate most strongly to ...postural control. It may be beneficial to include power or speed training into falls prevention programs.
Introduction
Post-menopausal women with low bone mass are at higher risk of bone fractures subsequent to falls. Understanding the correlates of postural control in this collective informs intervention design for falls prevention.
Methods
We examined postural control in single-leg stance on stable and unstable surfaces in 63 community-dwelling post-menopausal women with osteopenia or osteoporosis but without diagnosed neuromuscular, vestibular or arthritic diseases. Postural measures were compared to countermovement jump performance (height, force and power), leg-press strength (10 repetition maximum), calf muscle area and density (via peripheral quantitative computed tomography), body mass, height and age.
Results
On step-wise regression, peak countermovement jump power and jump height (
p
≤ 0.014), but not jump force, leg-press strength or calf muscle size, were related to postural control in single-leg stance on, respectively, an unstable surface (eyes open) and standing on a stable surface (eyes open). None of the parameters measured were significantly related to the postural control parameters in single-leg stance on a stable surface with eyes closed. With testing on the stable surface, body mass was associated with slow mean centre of pressure movement speed (
p
≤ 0.030).
Conclusions
Our findings show that, in post-menopausal women with low bone mass, neuromuscular power is a more important determinant of postural control than muscle strength or size. Our findings provide evidence to support the integration of power or speed training into falls prevention and balance training programs in post-menopausal women with osteopenia and osteoporosis.
Summary
In this 2-year extension of a 3-year study, bazedoxifene showed sustained efficacy in preventing new vertebral fractures in postmenopausal women with osteoporosis and in preventing ...non-vertebral fractures in higher-risk women. Bazedoxifene significantly increased bone mineral density and reduced bone turnover versus placebo and was generally safe and well tolerated.
Introduction
This study evaluated the efficacy and safety of bazedoxifene for the treatment of postmenopausal osteoporosis over 5 years.
Methods
A total of 4,216 postmenopausal women with osteoporosis were enrolled in this 2-year extension of a 3-year, randomized, double-blind, placebo-controlled, phase 3 trial. In the core study (
N
= 7,492), subjects received bazedoxifene 20 or 40 mg/day, raloxifene 60 mg/day, or placebo. The raloxifene arm was discontinued after 3 years; subjects receiving bazedoxifene 40 mg were transitioned to bazedoxifene 20 mg after 4 years. Five-year findings are reported for bazedoxifene 20 and 40/20 mg and placebo. Endpoints included incidence of new vertebral fractures (primary) and non-vertebral fractures, and changes in bone mineral density (BMD) and bone turnover markers.
Results
At 5 years, the incidence of new vertebral fractures in the intent-to-treat population was significantly lower with bazedoxifene 20 mg (4.5%) and 40/20 mg (3.9%) versus placebo (6.8%;
P
< 0.05), with relative risk reductions of 35% and 40%, respectively. Non-vertebral fracture incidence was similar among groups. In a subgroup of higher-risk women (
n
= 1,324; femoral neck T-score ≤−3.0 and/or ≥1 moderate or severe or ≥2 mild vertebral fractures), bazedoxifene 20 mg reduced non-vertebral fracture risk versus placebo (37%;
P
= 0.06); combined data for bazedoxifene 20 and 40/20 mg reached statistical significance (34% reduction;
P
< 0.05). Bazedoxifene significantly increased BMD and reduced bone turnover versus placebo (
P
< 0.05) and was generally safe and well tolerated.
Conclusions
The findings support a sustained anti-fracture effect of bazedoxifene on new vertebral fractures in postmenopausal osteoporotic women and on non-vertebral fractures in the higher-risk subgroup of women.
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 ≤ −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.
In this work we examine the reliability and validity (in comparison to magnetic resonance imaging; MRI) of real-time ultrasound measures of lumbar erector spinae thickness. We also consider the ...between-day reliability of the lumbar multifidus muscle area as measured via ultrasound. 23 male subjects aged 21-45 years were measured three times over the course of nine days by one operator. The first (L1) through to the fifth (L5) lumbar vertebral levels were measured on the left and right sides. MRI was performed on the same day as first ultrasound scanning. For between-day intra-rater reliability, intra-class correlation co-efficients (ICCs), standard error of the measurement, minimal detectable difference and co-efficients of variation (CVs) were calculated along with their 95% confidence intervals and Bland-Altman analysis was performed. On Bland-Altman analysis, erector spinae thickness and multifidus area ultrasound measures 'agreed' with equivalent MR measures, though the correlation between MR and ultrasound measures was typically poor to moderate. For both ultrasound measures, the ICCs ranged from 'moderate' to 'excellent' at individual vertebral levels, although multifidus area (CV ranged from 8 to 15%) was less reliable than erector spinae thickness (CV ranged from 6 to 10%). 'Agreement' on Bland-Altmann analysis was present between days for all ultrasound measures. Averaging between sides and between vertebral levels improved reliability. Average erector spinae thickness showed a CV of 5.5% (ICC 0.77) and average multifidus area 6.2% (ICC 0.80).
Abstract Mechanical loading is thought to be a determinant of bone mass and geometry. Both ground reaction forces and tibial strains increase with running speed. This study investigates the ...hypothesis that surrogates of bone strength in male and female master sprinters, middle and long distance runners and race-walkers vary according to discipline-specific mechanical loading from sedentary controls. Bone scans were obtained by peripheral Quantitative Computed Tomography (pQCT) from the tibia and from the radius in 106 sprinters, 52 middle distance runners, 93 long distance runners and 49 race-walkers who were competing at master championships, and who were aged between 35 and 94 years. Seventy-five age-matched, sedentary people served as control group. Most athletes of this study had started to practice their athletic discipline after the age of 20, but the current training regime had typically been maintained for more than a decade. As hypothesised, tibia diaphyseal bone mineral content (vBMC), cortical area and polar moment of resistance were largest in sprinters, followed in descending order by middle and long distance runners, race-walkers and controls. When compared to control people, the differences in these measures were always > 13% in male and > 23% in female sprinters ( p < 0.001). Similarly, the periosteal circumference in the tibia shaft was larger in male and female sprinters by 4% and 8%, respectively, compared to controls ( p < 0.001). Epiphyseal group differences were predominantly found for trabecular vBMC in both male and female sprinters, who had 15% and 18% larger values, respectively, than controls ( p < 0.001). In contrast, a reverse pattern was found for cortical vBMD in the tibia, and only few group differences of lower magnitude were found between athletes and control people for the radius. In conclusion, tibial bone strength indicators seemed to be related to exercise-specific peak forces, whilst cortical density was inversely related to running distance. These results may be explained in two, non-exclusive ways. Firstly, greater skeletal size may allow larger muscle forces and power to be exerted, and thus bias towards engagement in athletics. Secondly, musculoskeletal forces related to running can induce skeletal adaptation and thus enhance bone strength.
Summary
The effect of lumbar osteoarthritis on bone density and trabecular bone score (TBS) was evaluated cross-sectionally and prospectively in postmenopausal women. Lumbar spine osteoarthritis was ...graded according to Kellgren and Lawrence grades. Lumbar osteoarthritis was found to increase lumbar spine bone density, but not TBS.
Introduction
Lumbar osteoarthritis overestimates lumbar bone density (areal bone mineral density (aBMD)). A new texture parameter, the TBS, has been proposed. Calculation of aBMD uses grey level value, while TBS uses grey level variation. Therefore, our hypothesis was that TBS is not influenced by lumbar spine osteoarthritis.
Methods
Menopausal women participating in osteoporosis and ultrasound (OPUS) study were included. They had an aBMD measurement of the spine and hip at baseline and 6-year visit. TBS was calculated on lumbar spine dual-energy X-ray absorptiometry (DXA) scans in an automated manner. The presence of lumbar osteoarthritis was evaluated on baseline radiographs using Kellgren and Lawrence (K&L) classification. Grades range from 0 to 4. In our study, osteoarthritis was defined by at least K&L grade 2.
Results
This study included 1,254 menopausal women (66.7 ± 7.1 years). Among them, 727 attended the 6-year follow-up visit. Patients with lumbar osteoarthritis had an aBMD higher than those without lumbar osteoarthritis at the lumbar spine, but not at the hip. However, the aBMD significantly increased in all sites with the grade of K&L. In contrast, spine TBS was not different between patients with and without lumbar osteoarthritis (
p
= 0.70), and it was not correlated with K&L grade. Spine TBS and aBMD at all sites were negatively correlated with age (
p
< 0.0001). Body mass index was correlated positively with aBMD and negatively with spine TBS (
p
< 0.0001). The 6-year change of aBMD was significant in the hip and nonsignificant in the lumbar spine. That of TBS was significant, with a 3.3 % decrease (
p
< 0.0001), independent of K&L grade (
p
= 0.28).
Conclusion
In postmenopausal women, lumbar osteoarthritis leads to an increase in lumbar spine aBMD. In contrast, spine TBS is not affected by lumbar osteoarthritis.
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