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Biomedical subjects

Pierre D Delmas

Publications and source records attributed to Pierre D Delmas.

At least 55 records · Page 3Linked to original sources
PubMed2004

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

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

Aged↗
PubMed2004

Association between spine disc degeneration and type II collagen degradation in postmenopausal women: the OFELY study.

OBJECTIVE: To investigate whether radiologic spine disc degeneration is associated with increased type II collagen (CII) degradation products in the urine of postmenopausal women, independently of radiologic knee osteoarthritis (OA) and clinical hand OA. METHODS: The study group comprised 324 postmenopausal women ages 58-94 years who had no treatment or disease that could alter bone metabolism. Lateral radiographs of the thoracic and lumbar spine were obtained in each woman and scored for disc space narrowing (DSN) and osteophytes. Fixed-flexion posteroanterior radiographs of the knee were obtained to assess femorotibial knee OA. In all women, hand OA was assessed by clinical examination, and the level of urinary C-terminal crosslinking telopeptide of CII (CTX-II), a biologic marker of CII degradation, was measured. RESULTS: The prevalences of radiographic lumbar and thoracic spine disc degeneration, knee OA, and clinical hand OA were 84%, 88%, 35%, and 58%, respectively. After adjustment for age and body mass index (BMI), patients with lumbar spine DSN grade > or = 1 had, on average, 34% higher CTX-II levels compared with the other women (P = 0.0005), whereas no association was observed with lumbar spine osteophytes. No significant association between thoracic spine DSN or osteophytes and urinary CTX-II levels was observed. Multivariate analysis of variance showed that, after adjustment for age and BMI, lumbar spine DSN (P = 0.0049), knee OA (P = 0.0055), and clinical hand OA (P = 0.0060) were, independently of each other, associated with CTX-II levels. Thus, patients with lumbar spine DSN, knee OA, and clinical hand OA had CTX-II levels 80% higher (P < 0.0001 after adjustment for age and BMI) than those of patients with no lumbar spine DSN, no radiologic knee OA, and no clinical hand OA. CONCLUSION: Postmenopausal women with lumbar spine disc degeneration are characterized by increased CII degradation. The contribution of lumbar spine DSN to CII degradation was similar to, and independent of, the contribution of radiologic knee OA or clinical hand OA. Lumbar spine disc degeneration in elderly patients should be assessed when analyzing levels of CTX-II in studies of knee, hip, and hand OA.

Adult↗
PubMed2004

Changes in bone mineral density explain little of the reduction in vertebral or nonvertebral fracture risk with anti-resorptive therapy.

The structural basis for the reduction in vertebral and nonvertebral fracture risk in patients using anti-resorptive therapy is not well understood. As reduced bone mineral density (BMD) increases the risk for fracture and anti-resorptive agents increase BMD, it was commonly held that the increase in BMD explained the fracture risk reduction until several meta-analyses either failed to detect a significant association between vertebral fracture risk reduction and the incremental increase in BMD or reported that only a small proportion of the vertebral fracture risk reduction was explained by changes in BMD. Recently, it was reported that the risk of nonvertebral fractures decreased when an increase in BMD accompanied anti-resorptive treatment [J. Clin. Endrocrinol. Metab. 87 (2002) 1586]. However, a reanalysis of the data, using the same statistical methods after correcting for discrepancies in the reported BMD and person-year data, suggested that the magnitude of reductions in nonvertebral fracture risk was not associated with the magnitude of increases in BMD at the end of the first year or at completion of the studies. We infer that only a small proportion of risk reduction in vertebral and nonvertebral fractures observed with anti-resorptive drug therapy is explained by the increase in BMD. Further studies are needed to define the structural basis of the fracture risk reduction.

Bone Density↗
PubMed2004

Estimated number of women likely to benefit from bone mineral density measurement in France.

OBJECTIVES: To determine the number of women in France at least 50 years of age with risk factors for osteoporosis likely to lead to bone mineral density measurement, an investigation reimbursed by the French national health insurance system in patients at risk for osteoporosis. The study was commissioned by the French health authorities. MATERIALS AND METHODS: Risk factors for osteoporosis were defined as recommended by the French Agency for Accreditation and Evaluation in Health (ANAES) in 2001. The study data were from nine cohort studies done in France and from the National Health Insurance Agency for the Rhone-Alpes region of France. Risk factor prevalences in France were standardized by extrapolation according to the age distribution in France. RESULTS: Overall, data were collected in 123,986 women aged 50 years or older. From these data, risk factor estimates were as follows: menopause before 40 years of age, 1.5 million women; body mass index (BMI) lower than 19 kg/m(2), nearly 700,000; history of fracture, more than 2 million; history of femoral neck fracture in the mother, more than 1 million; history of health problems potentially responsible for osteoporosis, 400,000; and history of long-term glucocorticoid therapy, 612,000. In all, 3,186,318 (30%) women were estimated to have at least one risk factor and 785,512 (7.5%) at least two risk factors. CONCLUSIONS: Although our study sample was not representative of the population residing in France, the large sample size and diversity of data sources support the validity of our estimate of the prevalence of risk factors for osteoporosis in postmenopausal women living in France.

Absorptiometry, Photon↗
PubMed2004

Hormonal and lifestyle determinants of appendicular skeletal muscle mass in men: the MINOS study.

BACKGROUND: Aging-related sarcopenia is characterized by a loss of muscle mass and strength and increased fatigability. However, studies of its determinants in elderly men are scarce. OBJECTIVE: We investigated risk factors for sarcopenia in a large cohort of men. DESIGN: We analyzed 845 men aged 45-85 y who belonged to the MINOS cohort. Lifestyle factors (physical activity, tobacco smoking, alcohol intake, caffeine intake) were evaluated by using a standardized questionnaire. Appendicular skeletal muscle mass (ASM) was estimated by using dual-energy X-ray absorptiometry. The relative appendicular skeletal muscle mass index (RASM) was calculated as ASM/body height(2.3). Apparent free testosterone concentration (AFTC) and free testosterone index (FTI) were calculated on the basis of concentrations of total testosterone and sex hormone-binding globulin. RESULTS: RASM decreased with age (r = -0.29, P < 0.0001). Current smokers had lower RASM than did subjects who never smoked (-3.2%; P < 0.003). RASM increased with the intensity of physical activity at work (P for trend < 0.001). Men who participated in regular exercise during leisure time had 2.2% higher RASM than did those who did not (P < 0.03). Men whose values for AFTC, FTI, or 25-hydroxycholecalciferol [25(OH)D] were >2 SDs below the mean for young men had significantly lower RASM than did men with higher values. Men with sarcopenia, defined as the lowest quartile of RASM in the studied cohort (<6.32 kg/m(2.3)), were significantly older than men with normal RASM, weighed significantly less, smoked more, and spent significantly less time on leisure-time activities. Sarcopenic men also had lower values for testosterone, AFTC, FTI, and 25(OH)D. CONCLUSION: In elderly men, low physical activity, tobacco smoking, thinness, low testosterone (AFTC and FTI), and decreased 25(OH)D concentrations are risk factors for sarcopenia.

Aged↗
PubMed2004

Noninvasive techniques for assessing skeletal changes in inflammatory arthritis: bone biomarkers.

PURPOSE OF REVIEW: Inflammatory arthritis diseases including rheumatoid arthritis (RA) are characterized by systemic bone loss and increased risk of osteoporosis and local joint bone erosion. Clinical and biologic parameters of disease activity and inflammation and radiologic findings are poorly sensitive for assessing skeletal changes. More specific biologic markers reflecting systemic quantitative and dynamic changes of bone turnover represent promising adjunctive tools. RECENT FINDINGS: More specific and well-characterized biochemical assays especially for type I collagen-based bone resorption markers have been recently developed. Prospective studies indicate that increased levels of some biochemical markers of bone resorption are associated with a more rapid progression of joint destruction in patients with early RA, independently of disease activity and inflammation parameters. This increased bone resorption associated with local bone erosion is likely to be mediated by changes in the balance of the OPG/RANK-L system (receptor activator of nuclear factor kappaB-ligand and osteoprotegerin) as suggested by the significant association of this ratio in serum and long-term radiologic progression. Besides their well-documented response to bisphosphonate treatment used as adjuvant therapy in patients with glucocorticoid-induced osteoporosis, bone markers may be useful to assess potential beneficial effects of new disease-modifying antirheumatic drugs on systemic bone loss and on progression of joint damage. SUMMARY: Recent evidence suggests that biochemical markers of bone resorption may be useful to predict progression of joint damage in RA. Together with new biochemical markers of cartilage turnover, they are likely to play a major role in assessing effects of treatment on joint damage. Their value in assessing systemic and local bone abnormalities should be explored in other inflammatory arthritis diseases such as ankylosing spondylarthritis.

Arthritis↗
PubMed2004

Assessment of the role of 17beta-oestradiol in bone metabolism in men: does the assay technique matter? The MINOS study.

OBJECTIVE: 17Beta-oestradiol (17beta-E2), mainly its bioavailable fraction (bio-17beta-E2), is a determinant of bone mineral density (BMD) and bone remodelling in men. As direct measurement of bio-17beta-E2 is time-consuming, we compared the value of directly measured bio-17beta-E2 and of calculated bio-17beta-E2 and free 17beta-E2 by studying their association with BMD and markers of bone turnover in a cohort of men (MINOS). DESIGN: A cross-sectional study in which the association between BMD and bone markers, on the one hand, and serum levels of 17beta-E2, on the other, was analysed according to the levels of measured and calculated bio-17beta-E2 and free 17beta-E2 in a cohort of men. SUBJECTS: Men from the MINOS cohort including 87 men aged 19-45 to establish the reference control normal range of hormones and 637 men aged 50-85 (studied group). MEASUREMENTS: Total 17beta-E2, testosterone, SHBG and albumin were measured by standard methods. bio-17beta-E2 was directly measured after the precipitation of SHBG by ammonium sulfate. bio-17beta-E2 and free 17beta-E2 were calculated using serum SHBG and albumin levels as described by Sodegard et al. (J. Steroid Biochem., 16 (1982) 801). RESULTS: Calculated bio-17beta-E2 and free 17beta-E2 were correlated with measured bio-17beta-E2 and between themselves (r = 0.90-1.00, P < 0.0001). Calculated bio-17beta-E2 and free 17beta-E2 disclosed a similar association with BMD (difference between lowest and highest quartiles of 17beta-E2: 2.6-6.8%, P < 0.05-0.005) to that of measured bio-17beta-E2 (3.6-6.1%, P < 0.005-0.001). The association between bone markers levels and measured vs. calculated 17beta-E2 were also similar. Predictive accuracy for lowered BMD and elevated levels of biochemical bone markers (evaluated using receiver operating characteristics) was relatively low (area under curve -0.582 to 0.709) but similar for different forms of bioavailable and free 17beta-E2. CONCLUSIONS: In elderly men, the concentrations of bioavailable and free 17beta-E2, calculated using equations including either the measured albumin concentration or the constant albumin concentration of 43 g/l, can be used, at least in clinical studies, instead of the bio-17beta-E2 concentrations measured after ammonium sulfate precipitation.

Adolescent↗
PubMed2004

Comparison of fracture, cardiovascular event, and breast cancer rates at 3 years in postmenopausal women with osteoporosis.

OBJECTIVES: To compare event rates for osteoporotic fractures, cardiovascular events, and breast cancer in postmenopausal women with osteoporosis. DESIGN: A prospective, observational study of the placebo group in the double-blind, randomized Multiple Outcomes of Raloxifene Evaluation trial. SETTING: One hundred eighty clinical research centers in 25 countries. PARTICIPANTS: Postmenopausal women (n=2,565, mean age=67) with osteoporosis were given calcium (500 mg/d) and vitamin D (400-600 IU/d) supplements. MEASUREMENTS: The occurrence of at least one new fracture, cardiovascular event, or breast cancer diagnosis at 3 years was identified and adjudicated. RESULTS: The occurrence of any fracture was the most common event in these women. In women without prevalent vertebral fractures (n=1,627), the event rates per 1,000 patient-years were 45.4 for any fracture, 15.2 for vertebral fracture, 4.7 for clinical vertebral fracture, 0.9 for hip fracture, 8.3 for any cardiovascular event, and 5.2 for all breast cancer. In women with prevalent vertebral fractures (n=938), the event rates per 1,000 patient-years were 117.4 for any new fracture, 77.1 for new vertebral fracture, 25.7 for clinical vertebral fracture, 5.8 for hip fracture, 15.1 for any cardiovascular event, and 2.6 for all breast cancer. The effect of prevalent fracture status on event rates was not dependent on whether women were older or younger than 65, but women aged 65 and older had a 3.6 times greater occurrence of cardiovascular events than younger women, irrespective of prevalent fracture status. CONCLUSION: These data on the relative incidence of clinically significant skeletal and extra-skeletal outcomes may be useful in choosing an agent for health maintenance for postmenopausal women with osteoporosis.

Age Distribution↗
PubMed2004

Development and clinical application in arthritis of a new immunoassay for serum type IIA procollagen NH2 propeptide.

Type II collagen, the most abundant protein of cartilage matrix, is synthesized as a procollagen molecule including the N-(PIINP) and C-(PIICP) propeptides at each end. Type II procollagen is produced in two forms as the result of alternative RNA splicing. One form (IIA) includes and the other form (IIB) excludes a 69-amino acid cysteine-rich globular domain encoded by exon 2 in PIINP. During the process of synthesis, these N-propeptides are removed by specific proteases and released in the circulation, and their levels are believed to reflect type II collagen synthesis. In this chapter we describe the development of a specific enzyme-linked immunosorbent assay (ELISA) for the measurement of the IIA form of PIINP (PIIANP) in serum based on a polyclonal antibody raised against recombinant human exon 2 fusion protein of type II procollagen. We show that this ELISA is highly specific for circulating PIIANP and has adequate technical precision. In patients with knee osteoarthritis and rheumatoid arthritis, serum PIIANP was decreased by 53% (p < 0.0001) and 35% (p < 0.001), respectively, suggesting that type IIA collagen synthesis is altered in these arthritic diseases. The measurement of serum PIIANP may be useful for the clinical investigation of patients with joint diseases.

Adolescent↗
PubMed2003

Relationship between changes in biochemical markers of bone turnover and BMD to predict vertebral fracture risk.

UNLABELLED: The change in BMD is a poor predictor of vertebral fracture risk after raloxifene treatment. One-year percent change in bone turnover and BMD was used to predict vertebral fracture risk. The percent change in osteocalcin was determined to be a better predictor of vertebral fracture risk than BMD. INTRODUCTION: The association between baseline BMD and fracture risk is well understood. However, the relationship between changes in BMD and fracture risk is not well defined. It has previously been demonstrated that BMD change was a poor predictor of vertebral fracture risk in raloxifene-treated women, whereas bone turnover markers were significantly associated with fracture risk. In the current analysis, we explore the prediction of vertebral fracture risk using changes in both BMD and bone turnover. MATERIALS AND METHODS: The Multiple Outcomes of Raloxifene Evaluation (MORE) trial was a randomized, placebo-controlled trial of 7705 women with osteoporosis treated with raloxifene 60 or 120 mg/day for 3 years. Markers of bone turnover were measured in one-third of the study population (n = 2503), and the present analyses include these women. Logistic regression models were constructed using one-year percent changes in BMD and bone turnover and relevant baseline demographics to predict the risk of vertebral fracture with pooled raloxifene therapy at 3 years. All covariates were standardized before modeling to facilitate direct comparisons between changes in BMD and bone turnover. RESULTS AND CONCLUSION: Prevalent vertebral fracture status (p < 0.0001), baseline lumbar spine BMD (p < 0.0001), and number of years postmenopausal (p = 0.0005) were independent predictors of fracture risk in raloxifene-treated patients. Therapy-by-change in femoral neck BMD (p = 0.02) and therapy-by-change in osteocalcin (OC; p = 0.01) were also significant for all treatment groups, indicating that changes in BMD and OC have different effects on fracture risk for the placebo and pooled raloxifene groups. The final model included significant baseline variables and change in OC (p = 0.01), whereas change in femoral neck BMD was not significant. After adjustment of each significant baseline variable, the percent change in OC was better able to predict the reduction in vertebral fracture risk than the percent change in femoral neck BMD in patients treated with raloxifene.

Aged↗
PubMed2003

NMDA glutamate receptors are expressed by osteoclast precursors and involved in the regulation of osteoclastogenesis.

We previously identified functional N-methyl-D-aspartate (NMDA) glutamate receptors in mature osteoclasts and demonstrated that they are involved in bone resorption in vitro. In the present work, we studied the expression of NMDA receptors (NMDAR) by osteoclast precursors and their role in osteoclastogenesis using two in vitro models, the murine myelomonocytic RAW 264.7 cell line and mouse bone marrow cells, both of which differentiate into osteoclasts in the presence of macrophage colony-stimulating factor (M-CSF) and Rank ligand (RankL). Using RT-PCR analysis with specific probes, we showed that RAW 264.7 cells and mouse bone marrow cells express mRNA of NMDAR subunits NMDA receptor 1 (NR1) and NMDA receptor 2 (NR2) A, B, and D. These subunits are expressed all along the differentiation sequence from undifferentiated precursors to mature resorbing osteoclasts. Semi-quantitative PCR analysis showed no regulation of the expression of these subunits during the differentiation process. Two specific non competitive antagonists of NMDAR, MK801 and DEP, dose-dependently inhibited osteoclast formation in both models, indicating that osteoclastogenesis requires the activation of NMDAR expressed by osteoclast precursors. MK801 had no effect when added only during the first 2 days of culture, suggesting that NMDAR are rather involved in the late stages of osteoclast formation. Finally, we demonstrated using Western-blotting and immunofluorescence that activation of NMDAR in RAW 264.7 cells by specific agonists induces nuclear translocation of NF-kappa B, a factor required for osteoclast formation. Altogether, our results indicate that osteoclast precursors express NMDAR that are involved in the osteoclast differentiation process through activation of the NF-kappa B pathway.

Animals↗
PubMed2003

Recognizing and reporting osteoporotic vertebral fractures.

Vertebral fractures are the hallmark of osteoporosis, and occur with a higher incidence earlier in life than any other type of osteoporotic fractures. It has been shown that both symptomatic and asymptomatic vertebral fractures are associated with increased morbidity and mortality. Morbidity associated with these fractures includes decreased physical function and social isolation, which have a significant impact on the patient's overall quality of life. Since the majority of vertebral fractures do not come to clinical attention, radiographic diagnosis is considered to be the best way to identify and confirm the presence of osteoporotic vertebral fractures in clinical practice. Traditionally, conventional lateral radiographs of the thoracolumbar spine have been visually evaluated by radiologists or clinicians to identify vertebral fractures. The two most widely used methods to determine the severity of such fractures in clinical research are the semiquantitative assessment of vertebral deformities, which is based on visual evaluation, and the quantitative approach, which is based on different morphometric criteria. In our practice for osteoporosis evaluation we use the Genant semiquantitative approach: an accurate and reproducible method tested and applied in many clinical studies. The newest generation of fan-beam DXA systems delivering "high-resolution" lateral spine images offers a potential practical alternative to radiographs for clinical vertebral fracture analysis. The advantages of using DXA over conventional radiographic devices are its minimal radiation exposure and high-speed image acquisition. It also allows combined evaluation of vertebral fracture status and bone mass density, which could become a standard for patient evaluation in osteoporosis. The disadvantage of DXA use is that upper thoracic vertebrae cannot be evaluated in a substantial number of patients due to poor imaging quality. We truly believe that the that there is a major role for radiologists and clinicians alike to carefully assess and diagnose vertebral fractures using standardized grading schemes such as the one outlined in this review. Quantitative morphometry is useful in the context of epidemiological studies and clinical drug trials; however, the studies would be flawed if quantitative morphometry were to be performed in isolation without additional adjudication by a trained and highly experienced radiologist or clinician.

Absorptiometry, Photon↗
PubMed2003

Changes in bone mineral density following discontinuation or continuation of alendronate therapy in glucocorticoid-treated patients: a retrospective, observational study.

OBJECTIVE: To evaluate the effects of discontinuing or continuing alendronate (ALN) therapy on bone mineral density (BMD) after patients on a long-term regimen of glucocorticoids (GCs) completed a 1-year treatment period with ALN. METHODS: Eligible patients were individuals with GC-induced osteoporosis who had received ALN (5 or 10 mg) for 1 year in a prior clinical trial and, at the end of the year, were still taking GCs at an average daily dose of > or =7.5 mg of prednisone or equivalent. Patients were contacted 3-5 years after completion of the prior ALN trial for followup measurements of the lumbar spine BMD and hip BMD, and retrospective information was collected about serious or drug-related adverse experiences and concomitant medication use. Some patients remained on GCs, and some remained on ALN, either alone or in combination with other drugs. The primary response parameter was the percentage change in lumbar spine BMD from the end of year 1 to the followup visit. Change in BMD at the hip was a secondary response parameter. RESULTS: Ninety (49.2%) of the eligible 183 patients participated in the retrospective study. The followup period, which began at the end of year 1 of the original clinical trial, ranged from 3.3 years to 4.6 years. The mean number of days of treatment with ALN was 507. Fifty patients were included in the analysis because they had received supraphysiologic doses of GCs (doses above the lowest tertile of GC use for the study population; that is, higher than approximately 6 mg/day), and they had not taken (defined as <6 months of use) other bone-affecting agents except ALN. Eleven of the 50 patients discontinued taking ALN (duration of use <90 days), 8 took ALN between 90 days and 300 days, and 31 continued to take ALN for >300 days after year 1 of the clinical trial. GC users who discontinued treatment with ALN (<90 days of therapy) had numerically greater decreases in BMD at the lumbar spine, femoral neck, and total hip from the end of year 1 (mean change -5.1%, -9.2%, and -6.6%, respectively), compared with patients who continued to take ALN for >300 days (mean change 0.1%, -0.9%, and 1.8%, respectively). CONCLUSION: Substantial loss of BMD in the lumbar spine and hip was seen in patients who discontinued treatment with ALN but who continued to take >6 mg/day of GCs. However, patients receiving GCs who remained on the ALN regimen appeared to benefit from continued ALN treatment, since BMD was maintained in this latter group.

Adult↗
PubMed2003

Selective estrogen receptors modulators in the prevention and treatment of postmenopausal osteoporosis.

Raloxifene, the first of the second-generation of SERMs to be widely available, represents a significant improvement over tamoxifen. It prevents postmenopausal bone loss and reduces the incidence of vertebral fractures and of new breast cancer cases in osteoporotic patients without stimulating the endometrium. The suggestion that raloxifene could have a beneficial effect on cardiovascular disease in high-risk patients needs to be confirmed in prospective study. Selective estrogen receptors modulators represent a new and promising class of agents for the management of postmenopausal women with a scope that goes far beyond the prevention and treatment of osteoporosis. The observations that estrogens may play a role in bone metabolism of men and that SERMs prevent bone loss and induce a decrease in total serum cholesterol without affecting the prostate in orchidectomized male rats raises the possibility that they also may be of interest for the treatment of elderly men.

Aged↗
PubMed2003

Effect of withdrawal of hormone replacement therapy on bone mass and bone turnover: the OFELY study.

The beneficial effects of hormone replacement therapy (HRT) on bone mineral density (BMD) and bone turnover are well documented but whether HRT withdrawal is followed by an accelerated rate of bone loss is still controversial. We analyzed 26 women who have withdrawn HRT during a 6-year follow-up of the OFELY cohort. They were compared with three groups of women from the same cohort: one hundred four healthy postmenopausal women who continued HRT during the 6-year follow-up, 78 untreated postmenopausal women matched for age, and 31 untreated women within 5 years of menopause. Bone markers [serum osteocalcin (Intact OC), bone alkaline phosphatase (Bone ALP), and serum CTX] were performed annually during 4 years and bone mineral density (BMD) was measured at the forearm (DXA) during 6 years. Withdrawal of HRT was followed by a significant bone loss with an annual rate ranged from -0.7 to -1.6% at the radius according to the skeletal site and by a marked increase of bone markers after 6 months: +36 % for osteocalcin, +23% for bone alkaline phosphatase, and +120% for serum CTX (P < 0.05 to P < 0.001). In contrast, in the HRT continuing group, there was no bone loss and no substantial change of bone markers over 4 years. The rate of bone loss after withdrawal of HRT was significantly greater than in postmenopausal women matched for age who never received HRT (2.2 to 2.8 times higher according to the radius area) and not different as compared to the accelerated bone loss observed in untreated women within 5 years of menopause. We conclude that in postmenopausal women who have been on HRT for 6 years, cessation of treatment results in a rapid increase of bone turnover and a rate of bone loss similar to early postmenopausal women during the subsequent 4 years and greater than untreated women of the same age.

Adult↗
PubMed2003

Biomarkers in osteoarthritis.

PURPOSE OF REVIEW: Osteoarthritis is a chronic disease characterized by progressive destruction of articular cartilage and subchondral bone, and synovial reaction. Clinical and radiologic findings that form the basis of the diagnosis of osteoarthritis are poorly sensitive for monitoring the progression of the disease. Biologic markers reflecting quantitative and dynamic changes of joint tissue turnover represent promising adjunct tools. RECENT FINDINGS: New tissue-specific markers have been developed and include assays for type II collagen synthesis and degradation and synovitis. Prospective studies indicate that increased or decreased levels of some of these markers are associated with rapid progression of joint destruction in patients with knee osteoarthritis. Because progression of joint damage is likely to result primarily from an imbalance between degradation and reparative processes, a combination of markers reflecting these two components appears promising. For example, combining two new markers for type II collagen synthesis and degradation in an uncoupling index of cartilage turnover was more effective in predicting 1-year radiologic progression in knee osteoarthritis than the measurement of a single marker. Preliminary data in rheumatoid arthritis show a rapid response of a marker of type II collagen degradation under disease-modifying antirheumatic drugs, with early changes of this marker being predictive of long-term radiologic progression. SUMMARY: Recent evidence suggests that the combination of some biologic markers will be useful for identifying patients at risk for rapid joint destruction in osteoarthritis. Because of their rapid changes under treatment, biologic markers will play an important role in the development and monitoring of new structure-modifying therapies for osteoarthritis.

Biomarkers↗
PubMed2003

Long-term variability of markers of bone turnover in postmenopausal women and implications for their clinical use: the OFELY study.

UNLABELLED: Bone marker variability has raised concern for its use in individual patients. Serum osteocalcin (formation) and CTX (resorption) were measured every year for 4 years in 268 postmenopausal women. Seventy percent to 80% of women classified as having high bone turnover at baseline were similarly classified by the same methods 4 years later. INTRODUCTION: High bone marker levels are a risk factor for osteoporosis in postmenopausal women, but variability of measurements has raised doubts about their clinical use in an individual patient. METHODS: We studied 268 untreated postmenopausal women (50-81 years of age) belonging to a population-based prospective cohort. We collected fasting morning blood samples every year for 4 years to measure serum intact osteocalcin (OC) and serum C-terminal cross-linked telopeptide of type I collagen (CTX) as bone formation and resorption markers, respectively. RESULTS: Serum OC and CTX remained stable during follow-up (+ 1.2%/year, p = 0.003 and -0.13%/year, p = 0.70 for OC and S-CTX, respectively). At baseline, women were classified as having low (tertile 1), intermediate (tertile 2), or high (tertile 3) bone turnover. Agreement of classification between baseline and 4-year measurements was moderate (kappa [95% CI]: 0.51 [0.43-0.59] and 0.52 [0.44-0.60] for OC and S-CTX, respectively). Less than 10% of women in tertile 1 or 3 of either marker at baseline were found in the opposite tertile 4 years later. When the two markers were combined, only 2% of women at high turnover at baseline--defined as OC and/or S-CTX in tertile 3--were classified at low turnover 4 years later. Among women classified at high bone turnover at baseline (tertile 3), 70-80% were also found at high turnover 4 years later. Among women in tertile 2, only 51% and 43% for OC and CTX, respectively, remained in the same tertile at the second measurement. CONCLUSIONS: Serum levels of bone formation and resorption markers are stable over 4 years in postmenopausal women, on average. The majority of women classified as having high bone turnover were similarly classified by the same methods 4 years later. However, 20-30% of these women at risk for fracture would be incorrectly classified, suggesting that further investigation would be required to reduce the number of patients who would be treated unnecessarily if the decision was made on bone marker measurement. For women with intermediate levels, classification may be improved by a second measurement or by combining two markers.

Aged↗