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P D Delmas

Publications and source records attributed to P D Delmas.

At least 19 recordsLinked to original sources
PubMed2003

Role of vitamin D and parathyroid hormone in the regulation of bone turnover and bone mass in men: the MINOS study.

We investigated the role of vitamin D and of parathyroid hormone (PTH) in the regulation of bone mineral density (BMD), tone dimensions and seasonal variation of bone turnover in 881 men aged 19-85 years. Bone mineral content (BMC) and BMD of the lumbar spine, hip and whole body were measured with HOLOGIC 1000W and those of distal forearm with an OSTEOMETER DTX 100 device. Bone formation was evaluated using osteocalcin, bone alkaline phosphatase and N-terminal extension propeptide of type I collagen (PINP). Bone resorption was evaluated by 24-hour excretion of deoxypyridinoline and of C-terminal telopeptide of collagen type I. In young men (< 55 yrs) PTH level decreased with age (r = -0.18, P < 0.005) whereas 25-hydroxyvitamin D (25OHD) concentration was stable. In older men (> 55 years) 25OHD decreased whereas PTH increased with age (r = -0.27 and r = 0.21, P = 0.0001). In young men, 25OHD level varied with season but not PTH, biochemical markers of bone turnover nor BMD. In young men, 25OHD, but not PTH, was a significant determinant of BMC, cortical thickness and of biomechanical properties of the femoral neck. Biochemical bone markers and BMD were not correlated with PTH nor with 25OHD. In elderly men, winter levels of 25OHD were lowest whereas those of PTH, bone resorption markers and PINP were highest. After adjustment for age, body weight and season, biochemical markers of bone turnover were correlated with PTH. In elderly men, 25OHD and PTH were significant determinants of BMC, cortical thickness and of biomechanical parameters of the femoral neck. Men with vertebral deformities had lower concentrations of 25OHD, higher PTH levels and slightly elevated urinary excretion of biochemical markers of bone resorption compared with men without vertebral deformities. In conclusion, in young men, 25OHD discloses a seasonal variability in contrast to PTH and biochemical bone markers. In this group, 25OHD is a significant determinant of BMC and BMD but not of bone size. In elderly men, seasonal variation of 25OHD and PTH concentrations result in seasonal variation of bone resorption. In this group, both 25OHD and PTH are determinants of BMC and cortical thickness of the femoral neck and, consequently, of its mechanical parameters.

Adult↗
PubMed2003

Adverse effects of a SERM (Levormeloxifene). Safety parameters and bone mineral density 12 months after treatment withdrawal.

OBJECTIVE: Levormeloxifene is a selective estrogen receptor modulator (SERM). The development of the drug was discontinued due to intolerable adverse effects. This paper follow-up on the adverse events in a group of 234 women that was followed for 12 months without treatment after 12 months of treatment with levormeloxifene. METHODS: Adverse events were recorded at all clinical visits. The double-layer thickness of the uterine endometrium was determined by transvaginal ultrasonography. Endometrial biopsies were obtained by pipelle. The biopsies taken at the entrance to the follow-up phase were taken under hysteroscopy-guidance. Bone mineral density of the total body, lumbar spine (L1-L4), hip and forearm was measured by dual-energy X-ray absorptiometry. RESULTS: The most prominent adverse event was increased endometrial thickness over the pre-defined threshold of 8 mm. No cases of proliferative endometrium were reported. Following withdrawal of treatment the mean endometrial thickness approached baseline levels in a dose dependent manner. Hysteroscopic examinations showed that levormeloxifene was related to increased incidence of edema, vascularization and cysticity. In the levormeloxifene groups, a total of eight women had utero-vaginal prolapse and five women reported urinary incontinence (including worsening of a previously existing condition). Bone density in the spine and hip approached baseline levels during the 12 months of follow-up without treatment. CONCLUSION: Endometrial thickening, seen in association with the use of some SERM's, may lead to harmful adverse effects more than 12 months after treatment is initiated. Levormeloxifene prevents the postmenopausal bone loss, but the lowest effective dose is unknown.

Bone Density↗
PubMed2003

Independent predictors of all osteoporosis-related fractures in healthy postmenopausal women: the OFELY study.

Several epidemiological studies have identified clinical factors that predict the risk of hip fractures in elderly women independently of the level of bone mineral density (BMD), such as low body weight, history of fractures, and clinical risk factors for falls. Their relevance in predicting all fragility fractures in all postmenopausal women, including younger ones, is unknown. The objective of this study was to identify independent predictors of all osteoporosis-related fractures in healthy postmenopausal women. We prospectively followed for 5.3 +/- 1.1 years a cohort of 672 healthy postmenopausal women (mean age 59.1 +/- 9.8 years). Information on social and professional conditions, demographic data, current and past medical history, fracture history, medication use, alcohol consumption, caffeine consumption, daily calcium intake, cigarette smoking, family history of fracture, and past and recent physical activity was obtained. Anthropometric and total hip bone mineral density measurements were made. Incident falls and fractures were ascertained every year. We observed 81 osteoporotic fractures (annual incidence, 21 per 1000 women/year). The final model consisted of seven independent predictors of incident osteoporotic fractures: age > or = 65 years, odds ratio estimate (OR), 1.90 [95% confidence interval (CI) 1.04-3.46], past falls, OR, 1.76 (CI 1.00-3.09), total hip bone mineral density (BMD) < or = 0.736 g/cm(2), OR, 3.15 (CI 1.75-5.66), left grip strength < or = 0.60 bar, OR, 2.05 (CI 1.15-3.64), maternal history of fracture, OR, 1.77 (CI 1.01-3.09), low physical activity, OR, 2.08 (CI 1.17-3.69), and personal history of fragility fracture, OR, 3.33 (CI 1.75-5.66). In contrast, body weight, weight loss, height loss, smoking, neuromuscular coordination assessed by three tests, and hormone replacement therapy were not independent predictors of all fragility fractures after adjustment for all variables. We found that some--but not all--previously reported clinical risk factors for skeletal fragility predicted all fragility fractures independently of BMD in healthy postmenopausal women, although they differed somewhat from those predicting specifically hip fractures in elderly women. These risk factors appear to reflect quality of bone structure (previous fragility fracture), lifestyle habits (physical activity), muscle function and health status (grip strength), heredity (maternal history of fracture), falls, and aging. Measurements of these variables should be included in the clinical assessment of the risk of osteoporotic fractures in postmenopausal women.

Aged↗
PubMed2003

An immunoassay for type I collagen alpha 1 helicoidal peptide 620-633, a new marker of bone resorption in osteoporosis.

Type I collagen fragments are the most sensitive markers of bone resorption in osteoporosis. Currently, all available type I collagen-related bone resorption markers detect in serum and/or urine fragments arising from the telopeptide region of the molecule. Our aim was to evaluate the technical and clinical performances of a new assay detecting in urine a degradation fragment originating from the helical part of type I collagen and consisting of the 620-633 sequence of the alpha1 chain. Urinary helical peptide was measured with a new ELISA (Metra Helical peptide, Quidel Corporation). Results were compared with those of urinary C-terminal cross-linking type I collagen of type I collagen (CTX), an established bone resorption marker. We measured urinary helical peptide levels in 89 healthy women (age 31-89 years) and in 59 postmenopausal women involved in two randomized studies of the efficacy of alendronate (10 mg/day; n = 20) and transdermal 17beta estradiol (50 microg/day; n = 39). The within-run and between-run CVs were < or = 7.3 and 8.7%, respectively. In 59 healthy women, urinary helical peptide levels highly correlated with those of urinary CTX (r = 0.78, P < 0.0001). The long-term intraindividual variability assessed over 6 months in 18 untreated postmenopausal women was 24%. Compared to 24 premenopausal women, urinary helical peptide was 42% (P < 0.0001) higher in 65 postmenopausal women (mean age, 60 years), an increase comparable to that of urinary CTX (+ 47%, P < 0.0001). Urinary helical peptide levels decreased by 72% (P < 0.0001) after 3 months of alendronate treatment and by 59% (P < 0.0001) after 6 months of transdermal estrogen therapy. These changes were of similar magnitude to those of urinary CTX (-69 and -62%, respectively; NS compared with changes in helical peptide). In women treated with transdermal 17beta estradiol, the percentage of change of urinary helical peptide and urinary CTX at 6 months significantly correlated with the change in spinal bone mineral density after 2 years (r = -0.58, P = 0.002, and r = -0.52, P = 0.006, for urinary helical peptide and CTX, respectively). This new assay for type I collagen helical peptide has demonstrated adequate analytical performance and was highly correlated with urinary CTX, an established type I collagen C-telopeptide bone resorption marker. The test was a sensitive indicator of the antiresorptive effects of bisphosphonate and estrogens in postmenopausal women. This new bone resorption marker should be useful for the clinical investigation of patients with osteoporosis.

Adult↗
PubMed2003

Similar prevalence of vertebral fractures despite different approaches to define reference data.

Morphometric detection of vertebral fractures requires the use of reference normal values. In previous studies, normal values were obtained in young healthy adults or in adults of various ages in whom abnormal radiographs were excluded using trimming algorithms. We established four sets of normal values defined according to different approaches. We used a group of 102 young healthy women with normal spine radiographs and a population-based cohort of 260 women 51 to 85 years old (EVOS study) to select those with normal spine radiographs based on the semiquantitative method of Genant, the trimming algorithm defined by Melton, and the trimming algorithm defined by Black. Using the four sets of reference data, we applied two diagnostic criteria, the mean - 3SD and the 0.85 x mean to detect prevalent vertebral fractures in two groups of women: the population-based cohort of 260 women recruited for the EVOS study and 176 osteoporotic women 54 to 88 years old with at least one vertebral fracture. In the population-based cohort, the number of vertebral fractures varied from 53 to 57 for the 0.85 x mean cutoff and from 93 to 115 for the mean - 3SD cutoff. In the osteoporotic women, the number of vertebral fractures varied from 255 to 273 for the 0.85 x mean cutoff and from 372 to 404 for the mean - 3SD cutoff. In both groups, the number of vertebral fractures detected with the 0.85 x mean cutoff was close to the number detected by the semiquantitative method of Genant, which does not require a reference population. For the 0.85 x mean cutoff, agreement of diagnosis using different reference values was excellent (kappa = 0.96-0.99). For the mean - 3SD cutoff, agreement of vertebral fracture detection based on the four reference sets was good (kappa = 0.79-0.93). Agreement of diagnosis was lower when two cutoffs were compared using the same set of reference values (kappa = 0.60-0.81). In conclusion, reference data derived using different approaches give similar rates of prevalence of vertebral fractures. Compared to the semiquantitative assessment, the prevalence of vertebral fractures is similar for the 0.85 x mean cutoff, whereas it is considerably higher for the mean - 3SD cutoff.

Aged↗
PubMed2003

Urinary type II collagen C-telopeptide levels are increased in patients with rapidly destructive hip osteoarthritis.

OBJECTIVE: To compare type II collagen degradation using a new urinary specific marker in patients with rapidly destructive and those with slowly progressive hip OA. METHODS: Twelve patients with rapidly destructive and 28 patients with slowly progressive hip OA were included in a prospective, cross sectional case-control study. Urinary levels of C-terminal crosslinking telopeptide of collagen type II (CTX-II) as a marker of cartilage degradation were measured by an ELISA, and urinary free deoxypyridinoline (free DPD), a marker of bone resorption, was measured by high performance liquid chromatography. One x ray evaluation of the hips and urine samples was made in all patients when the diagnosis of OA was established. RESULTS: Patients with hip OA had higher mean (SD) urinary CTX-II levels than 65 healthy age matched controls (492 (232) v 342 (141), p<0.001), but no significant difference was seen for urinary free DPD (p=0.30). Increased urinary CTX-II, but not urinary free DPD, correlated significantly with decreased minimum joint space width assessed by radiograph of the hip. Mean urinary CTX-II levels were significantly higher in patients with rapidly progressive OA than in the slowly progressive group (612 (218) v 441 (221), p=0.015), whereas no significant difference of urinary free DPD was seen between the two groups (p=0.55). CONCLUSION: Patients with hip OA have increased CTX-II degradation as assessed by a new urinary marker. Increased urinary CTX-II levels are associated with rapidly destructive disease, suggesting that this marker might be useful in identifying patients with hip OA at high risk for rapid progression of joint damage.

Adult↗
PubMed2003

The type I collagen fragments ICTP and CTX reveal distinct enzymatic pathways of bone collagen degradation.

Bone resorption may generate collagen fragments such as ICTP and CTX, which can be quantified in serum and/or urine by using specific immunoassays, and which are used as clinical markers. However, the relative abundance of ICTP and CTX varies according to the type of bone pathology, suggesting that these two fragments are generated through distinct collagenolytic pathways. In this study, we analyzed the release of ICTP and CTX from bone collagen by the proteinases reported to play a role in the solubilization of bone matrix. Cathepsin K released large amounts of CTX, but did not allow a detectable release of ICTP. Conversely, the matrix metalloproteinases (MMPs) MMP-2, -9, -13, or -14 released ICTP, but did not allow a detectable release of CTX. Next we analyzed the release of ICTP and CTX from bone explants cultured in the presence of well-established inhibitors of these proteinases and of matrix solubilization. An inhibitor of cysteine proteinases including cathepsin K, inhibited the release of CTX, but not the release of ICTP. MMP inhibitors inhibited the release of ICTP, but also that of CTX, in agreement with the putative role of MMPs in the initiation of bone resorption in addition to matrix solubilization. Similarly the treatment of mice bearing bone metastasis with an MMP inhibitor led to a significant reduction of serum ICTP and CTX, and osteolytic lesions. We conclude that the generation of ICTP and CTX depends on different collagenolytic pathways. This finding may explain why these two markers may discriminate between different bone pathologies.

Aged↗
PubMed2003

Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate.

Changes in the level of biochemical markers of bone resorption with risedronate treatment for osteoporosis were examined as a surrogate for the decrease in fracture risk. Greater decreases in bone resorption markers were associated with greater decreases in vertebral (and nonvertebral) fractures. Antifracture efficacy of antiresorptive therapies is only partially explained by increases in bone mineral density. Early decreases in bone resorption may also play a role. We tested this hypothesis by measuring two bone resorption markers, the C-telopeptide of type I collagen (CTX) and the N-telopeptide of type I collagen (NTX), in osteoporotic patients in risedronate vertebral fracture trials. We studied 693 women with at least one vertebral deformity (mean age, 69 +/- 7 years) who received calcium (and vitamin D if required) and placebo or risedronate 5 mg daily for 3 years. The reductions in urinary CTX (median, 60%) and NTX (51%) at 3-6 months with risedronate therapy were significantly associated (p < 0.05) with the reduction in vertebral fracture risk (75% over 1 year and 50% over 3 years). The changes in both CTX and NTX accounted for approximately one-half (CTX, 55%; NTX, 49%) of risedronate's effect in reducing the risk of vertebral fractures in the first year and approximately two-thirds (CTX, 67%; NTX, 66%) over 3 years compared with placebo. The changes in CTX and NTX accounted for 77% and 54%, respectively, of risedronate's effect in reducing the risk of nonvertebral fractures over 3 years compared with placebo. The relationships between vertebral fracture risk and changes from baseline in CTX and NTX were not linear (p < 0.05). There was little further improvement in fracture benefit below a decrease of 55-60% for CTX and 35-40% for NTX. The decrease in bone resorption in patients taking risedronate accounts for a large proportion of the reduction in fracture risk. There may be a level of bone resorption reduction below which there is no further fracture benefit.

Aged↗
PubMed2002

Incidence of limb fracture across Europe: results from the European Prospective Osteoporosis Study (EPOS).

The aim of this population-based prospective study was to determine the incidence of limb fracture by site and gender in different regions of Europe. Men and women aged 50-79 years were recruited from population registers in 31 European centers. Subjects were invited to attend for an interviewer-administered questionnaire and lateral spinal radiographs. Subjects were subsequently followed up using an annual postal questionnaire which included questions concerning the occurrence of new fractures. Self-reported fractures were confirmed where possible by radiograph, attending physician or subject interview. There were 6451 men and 6936 women followed for a median of 3.0 years. During this time there were 140 incident limb fractures in men and 391 in women. The age-adjusted incidence of any limb fracture was 7.3/1000 person-years [pyrs] in men and 19 per 1000 pyrs in women, equivalent to a 2.5 times excess in women. Among women, the incidence of hip, humerus and distal forearm fracture, though not 'other' limb fracture, increased with age, while in men only the incidence of hip and humerus fracture increased with age. Among women, there was evidence of significant variation in the occurrence of hip, distal forearm and humerus fractures across Europe, with incidence rates higher in Scandinavia than in other European regions, though for distal forearm fracture the incidence in east Europe was similar to that observed in Scandinavia. Among men, there was no evidence of significant geographic variation in the occurrence of these fractures. This is the first large population-based study to characterize the incidence of limb fracture in men and women over 50 years of age across Europe. There are substantial differences in the descriptive epidemiology of limb fracture by region and gender.

Age Distribution↗
PubMed2002

The use of placebo-controlled and non-inferiority trials for the evaluation of new drugs in the treatment of postmenopausal osteoporosis.

Registration of new agents for the treatment of postmenopausal osteoporosis has been based over the past few years on placebo-controlled phase III trials with the incidence of patients with new vertebral/nonvertebral fractures as the most usual primary endpoint. The use of a placebo in diseases where an active treatment is available has been a matter of debate following the update of the Declaration of Helsinki by the World Medical Association which questioned this trial design. Current regulatory recommendations within the European Union suggest that placebo-controlled trials are still the best option when assessing the efficacy and safety of new drugs intended for the treatment of postmenopausal osteoporosis. This suggestion seems to be in apparent contradiction with the current content of the Declaration of Helsinki. This paper addresses the ethics and feasibility of placebo-controlled trials in the treatment of postmenopausal osteoporosis, in the light of available therapeutic options, and discusses possible alternative approaches in those patients where placebo treatment could be deemed to be unethical. It is concluded that placebo-controlled trials remain the most efficient design to establish the efficacy and safety of a new agent for the treatment of postmenopausal osteoporosis. Such trials are feasible and ethically acceptable in patients with osteoporosis but without prevalent vertebral fractures. Conversely, in patients with prevalent vertebral fractures, placebo-controlled trials are ethically questionable and non-inferiority trials are more appropriate. A relative margin of non-inferiority of 20-30% is suggested, to be discussed on a case by case basis.

Aged↗
PubMed2002

Is the predictive power of previous fractures for new spine and non-spine fractures associated with biochemical evidence of altered bone remodelling? The EPOS study. European Prospective Osteoporosis Study.

BACKGROUND: In the European Prospective Osteoporosis Study (EPOS), a past spine fracture increased risk of an incident fracture 3.6 - 12-fold even after adjusting for BMD. We examined the possibility that biochemical marker levels were associated with this unexplained BMD-independent element of fracture risk. METHODS: Each of 182 cases in EPOS of spine or non-spine fracture that occurred in 3.8 years of follow-up was matched by age, sex and study centre with two randomly assigned never-fractured controls and one case of past fracture. Analytes measured blind were: osteocalcin, bone-specific alkaline phosphatase, total alkaline phosphatase, serum creatinine, calcium, phosphate and albumin, together with the collagen cross-links degradation products serum CTS and urine CTX. Most subjects also had bone density measured by DXA. RESULTS: Cases who had recent fractures did not differ in marker levels from cases who had their last fracture more than 3 years previously. No statistically significant effect of recent fracture was found for any marker except osteocalcin, which was 17.6% lower in recent peripheral cases compared to unfractured controls (p<0.05) and this was independent of BMD. CONCLUSION: Past fracture as a risk indicator for future fracture is not strongly mediated through increased bone turnover.

Aged↗
PubMed2002

Different effects of antiresorptive therapies on vertebral and nonvertebral fractures in postmenopausal osteoporosis.

In postmenopausal osteoporosis, controlled clinical trials with antiresorptive therapies have shown consistent effects on vertebral fracture incidence while their effects on nonvertebral fractures, especially at the hip, have been reported with some agents, but not others. These discrepancies stress the differences in the pathogenesis of vertebral and nonvertebral fractures as discussed below, and the need to further investigate the mechanisms of action of various antiresorptive agents.

Bone Density↗
PubMed2002

The impact of osteoporosis on quality-of-life: the OFELY cohort.

Although the long-term outcomes of osteoporosis (Op) such as fracture, kyphosis, and pain are well known, the physical, psychological, and social consequences, beyond fracture and pain, are less clear. The Osteoporosis-targeted Quality-of-life (OPTQoL) questionnaire aimed at assessing the physical difficulty, fears, and adaptations to one's daily life was developed as a cross-sectional instrument to characterize the burden of Op within a community. The purpose of this study was to assess the impact of Op and related factors on community women participating in the OFELY study in France. Femoral neck bone mineral density (BMD) and OPTQoL questionnaire data were collected from women randomly selected from a large insurance company. Data were obtained for 756 women (mean age 59 years, range 36-92), most of whom were white. Women were classified into five groups based on the extent of physical manifestations and family history of Op. Women who had prior fractures, height loss, and/or kyphosis or both reported greater physical difficulty, more adaptations to their lives, and greater fears than women reporting no such changes. Scores on the Physical Difficulty domain, however, did not differ significantly based on BMD alone (BMD T score <or=2.5), after controlling for age and self-reported arthritis. The negative impact of Op on quality-of-life (QoL) seems to be more related to the physical manifestations of Op than to bone density levels. Recognition of the impact of Op-related factors on QoL may help health-care providers more fully appreciate the importance of prevention and treatment.

Adult↗
PubMed2002

Association between a functional interleukin-6 gene polymorphism and peak bone mineral density and postmenopausal bone loss in women: the OFELY study.

Genetic factors play an important role in determining bone mass and several genes are involved in this process. Interleukin-6 (IL-6) is a candidate gene for regulation of bone mineral density (BMD) and it has been suggested recently that novel IL-6 -174 G/C allelic variants may be associated with peak BMD in young men and with bone resorption in elderly women. In this study, we assessed the relationships between IL-6 gene polymorphism, peak BMD, rate of postmenopausal BMD loss, and bone turnover in women. BMD was measured by dual-energy X-ray absorptiometry in 255 healthy premenopausal women, aged 31-57 years. BMD loss at the forearm was measured over 4 years in 298 healthy untreated postmenopausal women, 50-88 years (mean 64 years). We also measured levels of serum osteocalcin, bone alkaline phosphatase, and N-propeptide of type I collagen for bone formation and three markers of bone resorption, including urinary and serum C-terminal cross-linking telopeptide of type I collagen and urinary N-terminal telopeptide of type I collagen, in both pre- and postmenopausal women at baseline. In premenopausal women we found a significant association between IL-6 genotypes and BMD at the whole body (analysis of variance [ANOVA], p = 0.03), femoral neck (p = 0.03), trochanter (p = 0.014), Ward's triangle (p = 0.03), and total hip (p = 0.006), with subjects having the CC genotype showing 3%-7% higher BMD levels than their GG counterparts. However, after matching women with CC and GG genotypes for body height the differences decreased (2%-4%), and were no longer significant (p = 0.10-0.23). In postmenopausal women the mean rate of loss at the ultradistal radius was significantly associated with IL-6 genotypes (ANOVA, p = 0.049), with women having the CC genotype showing a significantly greater rate of bone loss (p < 0.05) compared with their GC and GG counterparts. After adjustment for weight changes, the difference in the rate of ultradistal radius bone loss between genotypes decreased and was not significant (p = 0.06 for CC vs. GG). A similar trend was observed for distal radius bone loss (p = 0.10, ANOVA), but not for the middle radius. We found no significant association between genotypes, bone turnover markers in premenopausal women, and either bone turnover or BMD in postmenopausal women. We conclude that this new functional IL-6 polymorphism was weakly associated with level of peak BMD and the rate of forearm trabecular postmenopausal bone loss in this cohort of healthy French women. IL-6 genotypes accounted only for a small proportion of the interindividual variation of both peak BMD and rate of bone loss and were not significant after adjustment for height and changes in body weight, respectively, suggesting that part of the effect may have been due to the differences in body size. Larger long-term studies are necessary to assess adequately the relationships between IL-6 genotype, rate of bone loss, and risk of fracture.

Adult↗
PubMed2002

Falls explain between-center differences in the incidence of limb fracture across Europe.

There is important geographic variation in the occurrence of the major osteoporotic fractures across Europe. The aim of this study was to determine whether between-center variation in limb fracture rates across Europe could be explained by variation in the incidence of falls. Men and women, aged 50-79 years, were recruited from population-based registers in 30 European centers. Subjects were followed by postal questionnaire to ascertain the occurrence of incident fractures, and were also asked about the occurrence and number of recent falls. Self-reported fractures were confirmed, where possible, by review of the radiographs, medical record, or subject interview. The age- and gender-adjusted incidence of falls was calculated by center using Poisson regression. Poisson regression was also used to assess the extent to which between-center differences in the incidence of limb fractures could be explained by differences in the age- and gender-adjusted incidence of falls at those centers. In all, 6302 men (mean age 63.9 years) and 6761 women (mean age 63.1 years) completed at least one questionnaire concerning fractures and falls. During a median follow-up time of 3 years, 3647 falls were reported by men and 4783 by women. After adjusting for age and gender, there was evidence of significant between-center differences in the occurrence of falls. There was also between-center variation in the occurrence of upper limb, lower limb, and distal forearm fractures. Variation in the age- and gender-adjusted center-specific fall rates explained 24%, 14%, and 6% of the between-center variation in incidence of distal forearm and upper and lower limb fractures, respectively. Given the constraints inherent in such an analysis, in men and women aged 50-79 years, variation in fall rates could explain a significant proportion of the between-center variation in the incidence of limb fracture across Europe.

Accidental Falls↗
PubMed2002

Increased bone resorption in moderate smokers with low body weight: the Minos study.

Tobacco was found to be a risk factor for osteoporosis, mainly in postmenopausal women. We studied the effect of smoking on bone mineral density (BMD) and bone turnover in a cohort of 719 men, aged 51-85 yr, composed of 83 current smokers, 405 former smokers, and 231 men who never smoked. Most current and former smokers were moderate smokers (median, 10 cigarettes/d). Current smokers were younger, thinner, and drank more coffee and more alcoholic beverages. After adjustment for age, body weight, alcohol intake, and caffeine intake, current and former smokers had similar BMD, except at the forearm. Former smokers had lower BMD compared with never-smokers at most skeletal sites. Men who had smoked more than 7120 packs (third quartile) had lower BMD of total hip (P < 0.01) and distal forearm (P = 0.03) compared with men in the 2 lower tertiles. In the 3 groups, levels of bone formation markers did not differ. After adjustment for confounding variables, levels of urinary markers of bone resorption (beta-isomerized C-terminal telopeptide, free and total deoxypyridinoline) were higher in the current smokers than in former smokers and never-smokers. Concentrations of T, total 17beta-E2, and androstenedione were higher, whereas that of 25-hydroxyvitamin D was lower, in current smokers. When men were divided according to tertiles of body weight, increased bone resorption, decreased BMD and biochemical indexes of secondary hyperparathyroidism were observed in current smokers in the lowest tertile of body weight (<75 kg) compared with the never-smokers, but not in men in the two highest tertiles of body weight. Current smokers had a higher prevalence of vertebral deformities after adjustment for age and body weight (13% vs. 5%; P < 0.005). In summary, in moderate smokers with low body weight (<75 kg), increased bone resorption, not matched by increased bone formation, results in decreased BMD and an increased prevalence of vertebral deformities. In this group, low serum 25-hydroxyvitamin D and secondary hyperparathyroidism may explain, at least partly, the effect of tobacco on bone turnover. In former smokers, bone resorption is not increased, but BMD remains lower compared with that in never-smokers.

Aged↗
PubMed2002

Strontium ranelate: dose-dependent effects in established postmenopausal vertebral osteoporosis--a 2-year randomized placebo controlled trial.

The aim of the strontium ranelate (SR) for treatment of osteoporosis (STRATOS) trial was to investigate the efficacy and safety of different doses of SR, a novel agent in the treatment of postmenopausal osteoporosis. A randomized, multicenter, double-blind, placebo-controlled trial was undertaken in 353 osteoporotic women with at least one previous vertebral fracture and a lumbar T-score <-2.4. Patients were randomized to receive placebo, 0.5 g, 1 g, or 2 g SR/d for 2 yr. The primary efficacy endpoint was lumbar bone mineral density (BMD), assessed by dual-energy x-ray absorptiometry. Secondary outcome measures included femoral BMD, incidence of new vertebral deformities, and biochemical markers of bone metabolism. Lumbar BMD, adjusted for bone strontium content, increased in a dose-dependent manner in the intention-to-treat population: mean annual slope increased from 1.4% with 0.5 g/d SR to 3.0% with 2 g/d SR, which was significantly higher than placebo (P < 0.01). There was a significant reduction in the number of patients experiencing new vertebral deformities in the second year of treatment with 2 g/d SR [relative risk 0.56; 95% confidence interval (0.35; 0.89)]. In the 2 g/d group, there was a significant increase in serum levels of bone alkaline phosphatase, whereas urinary excretion of cross-linked N-telopeptide, a marker of bone resorption, was lower with SR than with placebo. All tested doses were well tolerated; the 2 g/d dose was considered to offer the best combination of efficacy and safety. In conclusion, SR therapy increased vertebral BMD and reduced the incidence of vertebral fractures.

Aged↗