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Biomedical subjects

Pierre Delmas

Publications and source records attributed to Pierre Delmas.

12 recordsLinked to original sources
PubMed2005

Pretreatment levels of bone turnover and the antifracture efficacy of alendronate: the fracture intervention trial.

UNLABELLED: The influence of pretreatment bone turnover on alendronate efficacy is not known. In the FIT, we examined the effect of pretreatment bone turnover on the antifracture efficacy of daily alendronate given to postmenopausal women. The nonspine fracture efficacy of alendronate was significantly greater among both osteoporotic and nonosteoporotic women with higher baseline levels of the bone formation marker PINP. INTRODUCTION: Previous trials have shown that high bone turnover is associated with greater increases in BMD among bisphosphonate-treated women. The influence of pretreatment bone turnover levels on antifracture efficacy has not been well studied. MATERIALS AND METHODS: We randomized women 55-80 years of age with femoral neck BMD T scores < or = -1.6 to alendronate (ALN), 5-10 mg/day (n = 3105), or placebo (PBO; n = 3081). At baseline, 3495 women were osteoporotic (femoral neck BMD T score < or = -2.5 or prevalent vertebral fracture), and 2689 were not osteoporotic (BMD T score > -2.5 and no prevalent vertebral fracture). Pretreatment levels of bone-specific alkaline phosphatase (BSALP), N-terminal propeptide of type 1 collagen (PINP), and C-terminal cross-linked telopeptide of type 1 collagen (sCTx) were measured in all participants using archived serum (20% fasting). The risk of incident spine and nonspine fracture was compared in ALN- and PBO-treated subjects stratified into tertiles of baseline bone marker level. RESULTS AND CONCLUSIONS: During a mean follow-up of 3.2 years, 492 nonspine and 294 morphometric vertebral fractures were documented. Compared with placebo, the reduction in nonspine fractures with ALN treatment differed significantly among those with low, intermediate, and high pretreatment levels of PINP levels (p = 0.03 for trend). For example, among osteoporotic women in the lowest tertile of pretreatment PINP (<41.6 ng/ml), the ALN versus PBO relative hazard for nonspine fracture was 0.88 (95% CI: 0.65, 1.21) compared with a relative hazard of 0.54 (95% CI: 0.39, 0.74) among those in the highest tertile of PINP (>56.8 ng/ml). Results were similar among women without osteoporosis at baseline. Although they did not reach statistical significance, similar trends were observed with baseline levels of BSALP. Conversely, spine fracture treatment efficacy among osteoporotic women did not differ significantly according to pretreatment marker levels. Spine fracture treatment efficacy among nonosteoporotic women was related to baseline BSALP (p = 0.05 for trend). In summary, alendronate nonspine fracture efficacy is greater among both osteoporotic and nonosteoporotic women with high pretreatment PINP. If confirmed in other studies, these findings suggest that bisphosphonate treatment may be most effective in women with elevated bone turnover.

Absorptiometry, Photon↗
PubMed2005

Recommendations for an update of the current (2001) regulatory requirements for registration of drugs to be used in the treatment of osteoporosis in postmenopausal women and in men.

Recent advances in the understanding of the epidemiology of osteoporosis suggest that certain parts of the current European guidelines for the registration of drugs in osteoporosis might be no longer substantiated. The object of this review is to provide the European regulatory authorities with an evidence-based working document providing suggestions for the revision of the "Note for guidance for the approval of drugs to be used in postmenopausal osteoporosis" (CPMP/EWP/552/95). Following an extensive review of the literature (1990-2004), the Group for the Respect of Ethics and Excellence in Science (GREES) organized a workshop including European regulators, academic scientists and representatives of the pharmaceutical industry. The outcomes of this meeting reflect the personal views of those who attended and should not, in any case, be seen as an official position paper of any regulatory agency. The group identified a certain number of points that deserve discussion. They mainly relate to the nature of the indication being granted to new chemical entities (treatment of osteoporosis in women at high risk of fracture instead of prevention and treatment of osteoporosis), the requirements of showing an anti-fracture efficacy on all or on major nonvertebral fractures (instead of the hip), the duration of pivotal trials (2 years instead of 3) and the possibility of considering bridging studies for new routes of administration, new doses or new regimens of previously approved drugs. The group also recommends that an indication could be granted for the treatment of osteoporosis in males on the basis of a placebo-controlled study, with bone mineral density changes after 1 year as the primary endpoint, for medications approved in the treatment of osteoporosis in women at high risk of fractures.

Female↗
PubMed2005

Predictive value of BMD for hip and other fractures.

UNLABELLED: The relationship between BMD and fracture risk was estimated in a meta-analysis of data from 12 cohort studies of approximately 39,000 men and women. Low hip BMD was an important predictor of fracture risk. The prediction of hip fracture with hip BMD also depended on age and z score. INTRODUCTION: The aim of this study was to quantify the relationship between BMD and fracture risk and examine the effect of age, sex, time since measurement, and initial BMD value. MATERIALS AND METHODS: We studied 9891 men and 29,082 women from 12 cohorts comprising EVOS/EPOS, EPIDOS, OFELY, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, DOES, Hiroshima, and 2 cohorts from Gothenburg. Cohorts were followed for up to 16.3 years and a total of 168,366 person-years. The effect of BMD on fracture risk was examined using a Poisson model in each cohort and each sex separately. Results of the different studies were then merged using weighted coefficients. RESULTS: BMD measurement at the femoral neck with DXA was a strong predictor of hip fractures both in men and women with a similar predictive ability. At the age of 65 years, risk ratio increased by 2.94 (95% CI = 2.02-4.27) in men and by 2.88 (95% CI = 2.31-3.59) in women for each SD decrease in BMD. However, the effect was dependent on age, with a significantly higher gradient of risk at age 50 years than at age 80 years. Although the gradient of hip fracture risk decreased with age, the absolute risk still rose markedly with age. For any fracture and for any osteoporotic fracture, the gradient of risk was lower than for hip fractures. At the age of 65 years, the risk of osteoporotic fractures increased in men by 1.41 per SD decrease in BMD (95% CI = 1.33-1.51) and in women by 1.38 per SD (95% CI = 1.28-1.48). In contrast with hip fracture risk, the gradient of risk increased with age. For the prediction of any osteoporotic fracture (and any fracture), there was a higher gradient of risk the lower the BMD. At a z score of -4 SD, the risk gradient was 2.10 per SD (95% CI = 1.63-2.71) and at a z score of -1 SD, the risk was 1.73 per SD (95% CI = 1.59-1.89) in men and women combined. A similar but less pronounced and nonsignificant effect was observed for hip fractures. Data for ultrasound and peripheral measurements were available from three cohorts. The predictive ability of these devices was somewhat less than that of DXA measurements at the femoral neck by age, sex, and BMD value. CONCLUSIONS: We conclude that BMD is a risk factor for fracture of substantial importance and is similar in both sexes. Its validation on an international basis permits its use in case finding strategies. Its use should, however, take account of the variations in predictive value with age and BMD.

Absorptiometry, Photon↗
PubMed2004

Osteoporosis and breast cancer.

Osteoporosis affects one in three women after the menopause and the incidence of osteoporotic fractures increases steadily throughout life. Breast cancer is the most common cancer in women, both before and after the menopause. In younger women, recovery from breast cancer has been achieved using aggressive chemotherapy and radiotherapy that can adversely affect bone tissue or induce premature menopause. In postmenopausal women, breast cancer and osteoporosis are common, and although both are dependent on estrogens this leads to conflicting implications for the diagnosis and treatment: estrogens reduce the risk of fractures but increase the risk of breast cancer. Estrogen supplementation is, therefore, contraindicated in patients with a history of breast cancer. Selective estrogen response modifiers (SERMs) hold great promise, as they decrease both the fracture risk via an estrogen-agonist effect on bone and the breast cancer risk via an estrogen-antagonist effect on the breast tissue. SERMs can be used after successful treatment for breast cancer. Bisphosphonates, which are potent bone resorption inhibitors, are widely used both in cancer patients and in the prevention and treatment of spinal and peripheral osteoporotic fractures. Contraindications are exceedingly rare, and the satisfactory safety profile of these agents can be expected to improve further with newly developed modes of administration. Whether the bisphosphonates currently used to treat osteoporosis (alendronate and risendronate) have beneficial effects on skeletal events related to cancer progression remains to be determined, however. In sum, selection of the optimal treatment for osteoporosis in a patient with breast cancer involves assessment of the risk/benefit ratio of each treatment option, based on patient age, other risk factors for osteoporosis, and the stage of breast cancer progression.

Adult↗
PubMed2004

Safety and efficacy of risedronate in reducing fracture risk in osteoporotic women aged 80 and older: implications for the use of antiresorptive agents in the old and oldest old.

OBJECTIVES: To determine the efficacy of risedronate in reducing vertebral fracture risk in women aged 80 and older with osteoporosis. DESIGN: Pooled analysis of data from three randomized, double-blind, controlled, 3-year-fracture-endpoint trials conducted from November 1993 to April 1998: Hip Intervention Program (HIP), Vertebral Efficacy with Risedronate Therapy-Multinational (VERT-MN), and VERT-North America (NA). SETTING: Office-based practices, research centers, and osteoporosis clinics in Europe, North America, and Australia. PARTICIPANTS: Osteoporotic (femoral neck bone mineral density T-score < -2.5 standard deviations or at least one prevalent vertebral fracture) women aged 80 and older. INTERVENTION: Patients received placebo (n=688) or risedronate 5 mg/d (n=704) for up to 3 years. All patients received 1,000 mg/d calcium and, if baseline levels were low, up to 500 IU/d vitamin D. MEASUREMENTS: Cumulative incidence of new vertebral fractures. RESULTS: After 1 year, the risk of new vertebral fractures in the risedronate group was 81% lower than with placebo (95% confidence interval=60-91%; P<.001). The number of women who needed to be treated to prevent one new vertebral fracture after 1 year was 12. This early onset of efficacy was consistent across the clinical programs, and antifracture efficacy was confirmed over 3 years. Risedronate was well tolerated, with a safety profile comparable with that of placebo. CONCLUSION: These findings provide the first evidence that, even in the very old, reducing bone resorption rate remains an effective treatment strategy for osteoporosis. Because each therapeutic agent used for the treatment of osteoporosis may have unique characteristics, the observations made in this study should not be assumed to apply to other bisphosphonates.

Aged↗
PubMed2003

Interest of biochemical markers of bone turnover for long-term prediction of new vertebral fracture in postmenopausal osteoporotic women.

OBJECTIVE: To analyse the interest of baseline levels and short-term (3-months) changes in serum osteocalcin (BGP), serum bone-specific alkaline phosphatase (BALP) and urinary C-telopeptide of type I collagen/creatinine ratio (U-CTX) to predict 3-years changes in bone mineral density (BMD) and spinal deformity index (SDI) in postmenopausal osteoporotic women. METHODS: Data were derived from a cohort of 603 osteoporotic women corresponding to the placebo arm of a 3-years prospective, double-blind study. RESULTS: Baseline values of BALP, BGP and U-CTX were negatively and significantly correlated with baseline spinal BMD. Significant correlations were also observed between the changes in BMD observed after 36 months at the spine and baseline BALP (r=0.20, P=0.0001), BGP (r=0.09, P=0.05) and U-CTX (r=-0.11, P=0.02). At 3 years, 71 women (15.9%) showed an increase in their SDI, corresponding to the occurrence of at least one new vertebral deformity. Baseline values of the four bone turnover markers (BTM) were not significantly related to the occurrence of new vertebral deformities. However, when considering the changes in the BTM observed after 3-months of follow-up, BGP (P=0.003) and U-CTX (P=0.047) were identified as significant predictors of an increase of SDI. The associated odds ratios (95% confidence interval (CI)) were 10.922 (2.218-53.78) for unit changes of log BGP and 1.369 (1.003-1.867) for unit changes of logU-CTX. The relative risk (RR) (IC 95%) of having a new vertebral fracture over 36 months was 0.31 (0.15-0.65) when being in the lowest quartile of 3-months changes in BGP as compared with the highest. CONCLUSION: We conclude that two sequential measurements of BGP and U-CTX performed at 3-months intervals could be of interest to identify postmenopausal osteoporotic women with the highest risk to present new vertebral deformities.

Aged↗
PubMed2003

Anatomic variations of the arteries of the nasal fossa.

OBJECTIVE: This study was performed for knowledge about the vascular supply of the nasal fossa and a description of the site of division and number of branches of the sphenopalatine artery. STUDY DESIGN: This study was performed on 10 fresh nonembalmed cadavers. Anatomic variations of nasal fossa arteries were studied. METHODS: First, 10 cephalic anatomic preparations were injected with red color latex into the right and left carotid arteries. Then, these specimens were sagittaly cut to dissect the sphenopalatine artery. Twenty vascularization cases were studied for the external branch of the sphenopalatine artery, and 10 cases were studied for the internal branch. RESULTS: The principal observations were: 1. the sphenopalatine artery division is 18 times in the infratemporal fossa and twice in the nasal fossa; 2. the nasopalatine artery supplies blood to the lower part of the septum and its anterosuperior area; and 3. the vascularization of the external wall is via the sphenopalatine artery through the arteries of the meatus and conchae. CONCLUSION: This study defines the vascular territories of the nasal fossa arteries and includes photographs of dissections.

Arteries↗
PubMed2003

[Impalpable testis: complete inguinal exploration by laparoscopy].

OBJECTIVE: To prospectively evaluate an inguinal approach to surgery for impalpable testis possibly assisted by laparoscopy during the same operation. MATERIAL AND METHODS: From January 1996 to March 2002 each case of unilateral impalpable testis was operated via an inguinal incision and laparoscopy was performed during the same procedure whenever the inguinal canal was devoid of any testicular structures. Sixty boys were included in this study. Anatomical features were evaluated and testes were classified according to their trophicity and their site. We evaluated the number of laparoscopies and the factors justifying this procedure. Orchidopexy was performed via an inguinal approach with extensive retroperitoneal dissection to release spermatic vessels, when necessary. A one-stage Fowler-Stephens operation was performed when the vascular pedicle remained too short despite this dissection. The results of orchidopexy were evaluated by physical examination with a minimum follow-up of 4 months. RESULTS: In this series of 60 cases, we identified 19 viable testes. Fourteen were situated in the abdomen, 3 in the inguinal canal, and 2 in a perineal ectopic position. The other cases were considered to present testicular atrophy. Laparoscopy was performed in 23 boys (38%) in whom no viable or atrophic testis was demonstrated via the inguinal incision. Sixteen of the 19 viable testes were descended by preserving the spermatic vessels with a good result. Two Fowler-Stephens operations gave a good result. One testis was removed. CONCLUSION: An inguinal incision, possibly completed by laparoscopy, appears to be a simple and reliable method of evaluation and treatment of impalpable testis.

Atrophy↗
PubMedDate not supplied

Trimegestone in a low-dose, continuous-combined hormone therapy regimen prevents bone loss in osteopenic postmenopausal women.

OBJECTIVE: To determine the efficacy of estrogen + progestogen therapy with 1 mg 17beta-estradiol and 0.125 mg trimegestone in the prevention of postmenopausal osteoporosis. DESIGN: For this study, 360 healthy, postmenopausal women with osteopenia [lumbar spine bone mineral density (BMD) between -1.0 and -2.5 SD of the premenopausal mean value] were enrolled in a 2-year prospective, randomized study, and 70% completed. Treatments were 1 mg 17beta-estradiol + 0.125 mg trimegestone (n = 179) or placebo (n = 181), given as daily oral therapy. All received a daily supplement of 500 mg calcium and 400 IU vitamin D. BMD measurements at the lumbar spine, total hip, and femoral neck as well as blood and urinary biochemical markers of bone turnover (serum osteocalcin), serum bone-specific alkaline phosphatase, serum CrossLaps, and urinary CrossLaps took place regularly. RESULTS: BMD increases relative to placebo were 6.3%, 3.9%, and 3.8% at the lumbar spine, total hip, and femoral neck, respectively (all P < 0.001). The biochemical markers of bone turnover were suppressed accordingly. Serum CrossLaps and urinary CrossLaps decreased rapidly, by 52% and 54%, respectively, whereas serum osteocalcin and serum bone-specific alkaline phosphatase revealed a more retarded decrease of 40% and 33%, respectively. Of the women receiving hormone therapy, 75% had amenorrhea from the first cycle, and 5% withdrew prematurely due to metrorrhagia or mastalgia. CONCLUSION: This new estrogen + progestogen therapy is efficient in increasing BMD in an osteopenic postmenopausal population. Furthermore, it is well tolerated, with few adverse events and an early bleeding control, which is likely to improve compliance to the treatment over the long term.

Administration, Oral↗