Biomedical subjects

S Goemaere

Publications and source records attributed to S Goemaere.

At least 19 recordsLinked to original sources

PubMed2005

Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) study.

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 > or = 74 yr and femoral neck bone mineral density T score < or = -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.

Aged↗

PubMed2005

Telomere length versus hormonal and bone mineral status in healthy elderly men.

Telomeres, the termini of linear chromosomes, exert a key role in the process of cellular ageing. Progressive telomere shortening is implicated in senescence in vitro and ample evidence exists to support the hypothesis that telomere length is correlated with chronological age and ageing phenotypes in vivo. In this study, we assessed whether mean telomere length of peripheral blood leukocytes predicts age-associated bone loss and/or is related to sex steroid status in an elderly healthy male population (71-86 years). Out of this population, we selected 110 samples for telomere restriction fragment (TRF) length analysis. Fasting blood was analysed for testosterone, estradiol, sex hormone binding globulin and biochemical markers of bone turnover. Also, the bioavailable fractions of sex steroids were calculated. Bone mineral density was measured at baseline and longitudinal follow-up was available for 84 men. We found that mean TRF length was inversely correlated with age (r=-0.19; P=0.049). Although no correlations were found with sex steroids or BMD at baseline, age corrected mean TRF length was associated with longitudinal bone loss for different distal forearm sites (P<0.05). Further studies are required to confirm our results, yet in this study, the predictive value of telomere length for bone loss appears to be substantial, hence underscoring the role of telomere length as a biomarker of ageing phenotypes.

Aged↗

PubMed2004

Seven years of treatment with risedronate in women with postmenopausal osteoporosis.

The effects of 7 years of risedronate treatment were evaluated in a second 2-year extension of a 3-year vertebral fracture study in women with osteoporosis. For the first 5 years of the study, women received risedronate 5 mg/day or placebo according to the original randomization, with maintenance of blinding. All the women who entered into the 6-7 years extension study received risedronate 5 mg/day. Endpoints included vertebral and nonvertebral fracture assessments, changes in biochemical markers of bone turnover, and bone mineral density (BMD) measurements. A total of 164 women (placebo/risedronate group, 81; risedronate group, 83) entered the 6-7 years extension study and 136 (83%) completed the study. Annualized incidence of new vertebral fractures during the 6-7 years was similar between the 2 treatment groups (3.8%). The incidence of vertebral fractures did not change in the 7-year risedronate group during the 6-7 years as compared to 4-5 years, while a significant reduction was observed in the placebo group that switched to risedronate treatment during years 6-7. The incidence of nonvertebral fractures was 7.4% and 6.0% in the placebo/risedronate and risedronate groups, respectively, during years 6-7. Urinary N-telopeptide decreased from baseline by 54% and 63% at 3 months and 7 years, respectively, in the risedronate group. The increases in BMD from baseline after 5 years of risedronate treatment were maintained or increased further during years 6-7; lumbar spine BMD after 5 and 7 years of risedronate treatment increased from baseline by 8.8% and 11.5%, respectively, for this extension study population. Risedronate was well tolerated and the occurrence of upper gastrointestinal adverse events was low. After 7 years of continuous risedronate treatment there were significant increases in BMD and decreases in bone turnover to within premenopausal levels and there was no indication of any loss of anti-fracture efficacy.

Aged↗

PubMed2004

Teriparatide effects on vertebral fractures and bone mineral density in men with osteoporosis: treatment and discontinuation of therapy.

Teriparatide (rhPTH[1-34]), a bone-forming agent for the treatment of osteoporosis, increases bone mineral density in men and women, and reduces the risk of fractures in women with osteoporosis. However, fracture efficacy has not yet been confirmed in men. Further, there is limited information on the effect of withdrawal of teriparatide. The purpose of this manuscript is to report on bone mineral density and vertebral fracture incidence during a 42-month observation period, from the baseline of the previously reported treatment study in men [1] through 30 months of posttreatment follow-up. Three hundred fifty-five men who were treated with once-daily self-injections of either placebo or 20 or 40 microg of teriparatide participated in the follow-up study. Bone mineral density gradually decreased following discontinuation of teriparatide therapy. However, the lumbar spine and total hip values remained significantly higher than baseline after 30 months of follow-up (p< or =0.001). Antiresorptive treatment prevented the decline and tended to further increase bone mineral density. Lateral thoracic lumbar radiographs obtained at baseline and 18 months after discontinuation of teriparatide were available for 279 men. Of these men, 11.7% assigned to placebo, 5.4% treated with teriparatide 20 microg, and 6.0% treated with teriparatide 40 microg had an incident vertebral fracture. In the combined teriparatide treated groups vs placebo, the risk of vertebral fracture was reduced 51% (nonsignificant, p=0.07). The incidence of moderate or severe fractures was significantly reduced by 83% (p=0.01). In conclusion, men who received teriparatide and who may have received follow-up antiresorptive therapy had a decreased risk of moderate and severe vertebral fractures.

Adult↗

PubMed2004

Perception of males' aging symptoms, health and well-being in elderly community-dwelling men is not related to circulating androgen levels.

Aging in men is associated with a progressive but variable decline in androgen production. In aging men there is also an increased occurrence of symptoms such as lack of concentration, nervousness, impaired memory, depressive mood, insomnia, lack of energy and general sense of well-being, decreased libido and erectile dysfunction, periodic sweating, bone and joint complaints, reduction of strength and increased adiposity. This ill-defined male climacterium syndrome is often referred to as "andropause", with the underlying implication that it is at least in part related to (relative) androgen deficiency. Recently an "aging males" symptoms' (AMS) rating scale was developed aimed at a more systematic description of severity of symptoms related to a clinically defined "male climacteric". We studied the relationship of male climacteric symptoms as assessed by the AMS with androgen levels and other questionnaires assessing the perception of health and well-being. Serum levels of sex steroids, sex hormone binding globulin and gonadotropins were measured in blood samples of 161 healthy, ambulatory, elderly men, aged 74-89 years who also completed the AMS scale. Mean value of total, free and bioavailable testosterone in this group was 401.6, 6.8 and 151.4 ng/dl, respectively, with 24.7, 32.4 and 52.2% of the values under the normal range for young men. The results of the AMS scores mostly suggested mild psychological and mild to moderate somatovegetative symptoms. However, clear sexual symptoms were reported in 88% of cases. None of the three AMS domain scale scores significantly correlated with testosterone, free testosterone or bioavailable testosterone. Significant correlations were observed between results for the AMS scores and those for other health questionnaires, but none of the subscores for the latter questionnaires correlated with androgen serum levels. In conclusion, the results of this study have shown that, as assessed by the AMS, healthy ambulatory elderly males over 70 had a high perception of sexual symptoms with mild psychological and mild to moderate somatovegetative symptoms. These data failed to support the view that in healthy elderly men, "climacteric symptoms" can predict androgen levels.

Aged↗

PubMed2004

Perturbed sex steroid status in men with idiopathic osteoporosis and their sons.

We reported previously that a gender-specific defect of acquisition of lumbar bone mass plays an important role in the pathogenesis of male idiopathic osteoporosis (IO) and that there is a strong heritability of this maturational defect, which is particularly manifest in sons of men with IO. A hypothetical role of an altered sex steroid status and/or of a (TTTA)(n)- repeat polymorphism of the aromatase (CYP19) gene in male IO remains to be established. We evaluated bone mineral density (BMD) at the lumbar spine and femoral neck in 64 male IO probands (selected on the basis of a z-score of -2 or less), 21 of their sons, 41 of their brothers, and 126 healthy, age-matched controls. Serum testosterone (T), estradiol (E(2)), and SHBG levels were measured by immunoassays. Free T (FT) and free E(2) (FE(2)) levels were calculated from total T, E(2), SHBG, and albumin concentrations using a previously validated equation. Probands, sons, and brothers had lower body weight than age-matched controls, with mean differences of 5.0, 4.6, and 4.0 kg, respectively. In probands, sons, and brothers, SHBG levels were higher compared with controls. Significantly lower FE(2) levels were observed in probands and sons compared with their respective controls (P < 0.05 and P < 0.01, respectively). The brothers had nonsignificantly lower FE(2) levels compared with their controls. In the total group of sons with significantly lower FE(2) levels, tertile analysis according to lumbar spine BMD showed that only in the subgroup of sons belonging to the lowest tertile both FE(2) and FT were decreased compared with their controls. The differences in FE(2) levels in IO probands and their sons remained significant after adjustment for body mass index (BMI), even though in multivariate analyses BMI was a major determinant of BMD. The frequency distribution of the CYP19 gene (TTTA)(n)- repeat length (determined by fragment analysis, GeneScan) was not different between men with IO and their controls. In conclusion, the finding of a relative FE(2) deficit in both men with IO as well as their affected sons, even after adjustment for BMI, suggests that estrogen-related perturbances may be involved in the pathogenesis of the deficient acquisition of peak bone mass in male IO.

Adult↗

PubMed2004

Hormonal and genetic determinants of bone loss in community-dwelling elderly men: a longitudinal population study.

In community-dwelling elderly men over age 70 years, BioE2 was positively associated with prospectively assessed BMD changes over 4 years. The CYP19 (TTTA)n-repeat polymorphism was, moreover, an additional independent determinant of BMD changes at the distal forearm. Furthermore, the CYP19 genotype was associated with self-reported clinical fracture status. The present analyses add further evidence to the view that serum BioE2 is a determinant of bone mass in elderly men and provides an indication that the aromatase enzyme may exert a direct modulatory action on bone metabolism at the tissue level in ageing men.

Aged↗

PubMed2003

Incidence of nonvertebral fractures in relation to time on treatment and bone density in glucocorticoid-treated patients: a retrospective approach.

The effects of duration of treatment and bone mineral density (BMD) on nonvertebral fracture in 560 glucocorticoid users were examined by using baseline and retrospective data from 2 parallel studies assessing the efficacy and safety of alendronate therapy. Baseline spine and hip BMD were significantly (P < 0.01) lower with increased time spent receiving glucocorticoids. Forty-three patients (7.7%) had experienced at least 1 nonvertebral fracture after starting glucocorticoid treatment. The hazard function for nonvertebral fracture occurrence increased significantly (P < 0.01) with time spent receiving glucocorticoids: fracture incidence per 1,000 person-years on glucocorticoids was 18 (< 5 years), 31 (5-10 years), and 35 (> 10 years). Patients with a history of nonvertebral fractures after starting glucocorticoid treatment had significantly lower lumbar spine (P < 0.01) and hip (< 0.01) BMD value than those without fractures. This retrospective analysis suggests that a BMD measurement of spine and hip may identify risk for nonvertebral fractures in a heterogeneous population of glucocorticoid users.

Journal Article↗

PubMed2003

Testicular volume in relation to hormonal indices of gonadal function in community-dwelling elderly men.

Aging is accompanied by involutional changes in testicular function; limited data suggest a decrease in bilateral testicular volume (BTV). We studied BTV by ultrasonography in relation to serum gonadal hormones in 115 healthy elderly men (median age, 78 yr) and 42 young men (median age, 26.5 yr). Elderly men had a clearly smaller BTV (mean, 20.6 vs. 29.7 ml; P < 0.001), whereas serum inhibin B was slightly but significantly decreased (mean, 176.8 vs. 212.8 ng/liter; P = 0.04); lower values in the elderly were observed for bioavailable (Bio) testosterone (T), Bio 17 beta-estradiol, inhibin B/FSH (mean, 18 vs. 58 ng/mU; P < 0.001), and T/LH ratios. In the elderly and the young, respectively, BTV was associated with inhibin B (r = 0.53, P < 0.001; r = 0.41, P < 0.01), FSH (r = -0.53, P < 0.001; r = -0.48, P < 0.01), and inhibin B/FSH ratio. Only in the old men was BTV significantly associated with LH (r = -0.32; P < 0.001), Bio T (r = 0.26; P < 0.01), and T/LH (r = 0.48; P < 0.001). In a multivariate analysis, FSH, inhibin B, and Bio T were independently associated with BTV in the elderly (R(2) = 0.34). Receiver operating characteristics curve analysis indicated that BTV at a criterion value of 14.3 ml had a sensitivity of 46% and a specificity of 79% to predict low serum Bio T levels in the elderly. In conclusion, the moderately decreased BTV observed in elderly men, strongly associated with a decrease of the inhibin B/FSH ratio, is consistent with a reduced Sertoli cell mass, compensated by increased FSH stimulation resulting in only limited decrease of Sertoli cell function. Finding of a low testicular volume in elderly men can contribute to the diagnosis of hypogonadism, but this criterion has low sensitivity to detect decreased T production.

Adult↗

PubMed2003

Bioavailable estradiol and an aromatase gene polymorphism are determinants of bone mineral density changes in men over 70 years of age.

The question of whether and to what extent the sex steroid deficiency in elderly men contributes to the pathogenesis of bone loss has not been fully explored. The aim of the present study was to assess the association of serum bioavailable (Bio) estradiol (E(2)) with the evolution of bone mineral density (BMD) in 214 community-dwelling men aged 71-86 yr as well as the possible modulation of estrogen effects by a tetranucleotide (TTTA)(n)-repeat polymorphism of the CYP19 gene, which encodes the aromatase enzyme that converts androgens into estrogens. BMD was measured at yearly intervals over a period of 4 yr using dual x-ray absorptiometry. Fasting blood was analyzed at baseline for testosterone (T), E(2), and SHBG; the respective bioavailable fractions, BioT and BioE(2), were calculated. Serum BioE(2) was associated with baseline BMD at different assessed skeletal sites, with correlation coefficients ranging between 0.23 and 0.37 (P < 0.001). Estimated annual percentage change of BMD (%BMD) was -0.39% [95% confidence index (CI), -0.56, -0.22] at the total hip, -0.04% (95% CI, -0.29, 0.21) at the femoral neck, and -0.37% (95% CI, -0.45, -0.29) at the total distal forearm. Higher circulating BioE(2) levels were associated with less bone loss at the forearm and the hip (P < 0.05). The CYP19 gene (TTTA)(n)-repeat length (determined by fragment analysis) was not associated with baseline BMD in the total group of elderly men. However, a significant association was observed between the CYP19 genotype and BMD change at the distal forearm; the highest bone loss was observed in subjects homozygotic for the shortest observed allele length of (TTTA)(7)-repeats (P < 0.02). The CYP19 (TTTA)(n)-repeat length was not associated with either baseline BioE(2) or the BioT/BioE(2) ratio. In multiple linear regression models, the CYP19 genotype and serum BioE(2) were determinants of %BMD change at the forearm (P < 0.05). No significant contribution of BioT to %BMD change was evident. As to fracture risk, the allele containing the shortest (TTTA)(n)-repeat length was more represented not only in elderly men with a positive personal fracture history (Pearson's chi(2) test = 4.03; df = 1; P = 0.05) but also in study subjects with a positive fracture history in their first-degree relatives (Pearson's chi(2) test = 6.48; df = 1; P = 0.01). In conclusion, the results of this prospective observational study support the view that BioE(2) is a determinant of bone density changes in elderly men and, furthermore, provide an indication that the aromatase enzyme may exert a direct modulatory action on bone metabolism at the tissue level in elderly men.

Aged↗

PubMed2003

Deficient acquisition of bone during maturation underlies idiopathic osteoporosis in men: evidence from a three-generation family study.

To address the issue whether deficient acquisition of bone during maturation or adult-onset bone loss is primarily to blame for idiopathic osteoporosis in men, we assessed indices of bone mineral density and size, as well as biochemical markers of bone turnover in 61 probands (ages 20-65 years) with idiopathic osteoporosis (z-score < or = -2.0 at the spine or hip), their first-degree relatives (n = 130), and age-matched controls. There was no indication of accelerated bone loss. Indeed, in probands, the observed bone deficit versus controls was unrelated to the age of probands, and indices of bone turnover were not significantly different from controls. On the other hand, a specific deficit in bone acquisition was suggested by findings of lower bone mineral density values in three generations of male and female relatives of the probands, including their offspring; bone turnover in relatives was not different from controls. The bone mineral density deficit was more pronounced in male compared with female relatives; approximately 60% of the sons had a spinal bone mineral density z-score of less than -2.0. There also was a skeletal site-specificity in probands and their male relatives with a larger areal bone mineral density deficit at the spine compared with the hip and the forearm. The deficit at the spine corresponded to a reduction of both volumetric bone mineral density and bone size; a similar less pronounced deficit in volumetric bone mineral density, but not in bone size, was observed at the femoral neck. These findings in probands and their first-degree relatives point toward a major contributory role of a genetically determined maturational defect in bone acquisition in the pathogenesis of idiopathic osteoporosis in men.

Adult↗

PubMed2002

Interest of a prescreening questionnaire to reduce the cost of bone densitometry.

Bone mineral density (BMD) measurement is widely recognized as the best single tool to identify patients with a high lifetime risk of developing an osteoporosis-related fracture. However, the cost/benefit value of screening the whole population has been repeatedly challenged and demonstrated to be rather poor. In many countries, BMD scan is not or no longer reimbursed because of lack of validated criteria to identify patients who should benefit from this procedure. Based on the proposals of a nationwide expert panel, a simple questionnaire identifying historical, clinical and behavioral risk factors for osteoporosis was developed. The aim of this study was to assess the diagnostic accuracy of the proposed criteria; to determine the extent to which this questionnaire could be useful for optimizing the use of densitometry tests; and, more specifically, to estimate the diagnostic costs per osteoporotic or osteopenic patient detected. For this purpose, we applied the questionnaire to 3998 consecutive individuals at least 20 years old, of both genders, either consulting spontaneously or referred for a BMD measurement to an outpatient osteoporosis center. BMD was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and at the hip (both total hip and femoral neck). Diagnostic accuracies were evaluated through measures of sensitivity, specificity, and positive and negative predictive values. After determining a benchmark value for age, different strategies were compared in order to identify the most cost-effective one in terms of cost per patient detected. According to the WHO operational definition of osteoporosis (T-score <-2.5), 31% of the subjects were classified as osteoporotic at one or more of the measured sites. If only patients with at least one of the proposed risk factors had been referred for scans, 33.3% of the BMD measurements would have been avoided. Among those, less than 5% were missclassified as they did have osteoporosis at the total hip and up to 23% at one or more of the considered sites. On the other hand, of the subjects who would be recommended for a densitometry test, only a small fraction were identified correctly (the positive predictive values varied from 11.3% at the total hip to 34.8% at any site). In this first setting, the suggested criteria seem useful chiefly for excluding subjects who do not need a DXA scan rather than selecting osteoporotic patients. When applied only to patients aged 61 years or more, the positive predictive values rose to 15.1% (total hip) and 42.9% (any site), whereas the corresponding negative predictive values were set at 93% and 68.6%. In comparison, with a mass screening scenario the estimated diagnostic costs (costs associated with the DXA procedure) per osteoporotic patient detected at any of the considered sites would be reduced by more than 9% (59.4 instead of 65.3 Euros) if the suggested indications are taken into account for prescreening patients. And when the questionnaire is applied only to women over the age of 60 years these costs would be further reduced to 50.6 Euros, representing a 23% decrease. Then, a prescreening strategy based on these indications concomitantly with an age-selective criterion could represent a promising way toward a more rational use of BMD measurement.

Absorptiometry, Photon↗

PubMed2002

Systems to assess the progression of finger joint osteoarthritis and the effects of disease modifying osteoarthritis drugs.

Our objective was to assess the progression of osteoarthritis (OA) using scoring systems based on the anatomical changes recorded in the finger joints on standard radiographs and to test how far these scoring systems could be used to evaluate the effects of candidate "disease modifying osteoarthritis drugs" (DMOAD). The appearance and growth of osteophytes, narrowing of the joint space and subchondral bone changes allowed the classic OA-associated anatomical lesions to be used to score the progression of finger joint OA. Progression of OA in the finger joints was also assessed by the their evolution through previously described and predictable anatomical phases on standard X-rays. These phases were characterised by complete loss of the joint space preceding or coinciding with the appearance of subchondral cysts eroding the entire subchondral plate, and have been described in "inflammatory" or "erosive" OA. The erosive episodes were followed by processes of remodelling. In order to interfere with the progression of osteoarthritis, two chondroitin sulphates with possible DMOAD effects were used in two series of patients with OA of the finger joints. The patients were included in two separate randomised, double-blind placebo-controlled trials: 46 of them received chondroitin polysulphate and 34 received chondroitin sulphate. Eighty-five patients were kept on placebo medication and were used as controls. All 165 patients were followed for 3 years. Posteroanterior X-rays of the metacarpophalangeal and interphalangeal (IP) finger joints were obtained at the start of this prospective study and at yearly intervals thereafter. Almost 80% of the distal IP and 50% of the proximal IP were affected at study entry. In approximately 40% of the patients the classic picture of OA of the IP joints was complicated by manifest erosive OA changes. The two systems to score the progression of OA (Anatomical Lesion and Anatomical Phase Progression Score System) showed definite progression within 3 years of follow-up, especially in the IP joints. When compared with the placebo controls, none of the chondroitin sulphates prevented OA from occurring in previously normal finger joints. However, when the classic OA-associated anatomical lesions were considered, OA was less progressive in both active treatment groups. Furthermore, fewer patients from both chondroitin sulphate- and chondroitin polysulphate-treated groups developed "erosive" osteoarthritis. In conclusion, conventional radiographs can be used to assess the morbidity and progression of hand OA. The systems used to score the progression of finger joint OA allowed the DMOAD effects of both chondroitin sulphates to be evaluated. The data recorded during these pilot studies should help investigators to design future long-term clinical experiments.

Adult↗

PubMed2002

Vitamin D receptor gene allelic variants, bone density, and bone turnover in community-dwelling men.

The role of vitamin D receptor (VDR) gene polymorphisms in the determination of bone mass and bone turnover is controversial in women. The aim of the study was to determine whether VDR polymorphisms are associated with indices of bone mineral density (BMD) (by dual-energy X-ray absorptiometry and by ultrasound) and/or with bone turnover and muscle strength, factors related to both BMD and fracture risk. For this purpose, we investigated a cohort of community-dwelling men >70 years (n = 271) and a group of healthy control subjects between the ages of 20 and 50 years (n = 137). VDR TaqI, ApaI, and FokI genotypes were determined using enzymatic restriction digestion of polymerase chain reaction (PCR) fragments. In the elderly group, the lowest BMD value at the femoral neck and at the calcaneus was observed in subjects with the "At-At" haplotype genotype, with differences between extreme haplotype groups ("At-At" vs. noncarriers of the "At" allele) ranging from 5.8% to 34.3% (p < or = 0.05). Moreover, at the different subregions of the distal forearm and the tibia, the lowest BMD estimates were consistently associated in both elderly and younger men with the "At" haplotype allele, although this did not approach statistical significance. Elderly subjects with the "At-At" genotype had a significantly higher serum osteocalcin level. BMD was not significantly related to the FokI VDR polymorphism at any of the assessed skeletal sites, nor were any of the biochemical markers associated with the FokI VDR genotype. There were no differences between genotype groups for any of the indices of muscle strength. The present study indicates that the VDR genotype is associated with BMD in healthy community-dwelling elderly men and tends to be associated with biochemical markers, particularly of bone formation, in elderly men.

Adult↗

PubMed2002

Estradiol in elderly men.

The role of estrogens in male physiology has become more evident, as a consequence of the discovery of human models of estrogen deficiency such as estrogen resistance or aromatase deficiency. In males, testosterone is the major source of plasma estradiol, the main biologically active estrogen, only 20% of which is secreted by the testes. Plasma estrone, 5% of which is converted to plasma estradiol, originates from tissue aromatization of, mainly adrenal, androstenedione. The plasma concentration of estradiol in males is 2-3 ng/dl and its production rate in blood is 25-40 micrograms/24 h; both of these values are significantly higher than in postmenopausal women. Plasma levels of estradiol do not necessarily reflect tissue-level activity as peripherally formed estradiol is partially metabolized in situ; thus, not all enters the general circulation, with a fraction remaining only locally active. Of the factors influencing plasma estradiol levels, plasma testosterone is a major determinant. However, the age-associated decrease in testosterone levels is scarcely reflected in plasma estradiol levels, as a result of increasing aromatase activity with age and the age-associated increase in fat mass. Free and bioavailable estradiol levels do decrease modestly with age as does the ratio of free testosterone to free estradiol, the latter testifying to the age-associated increased aromatization of testosterone. Estradiol levels are highly significantly positively related to body fat mass and more specifically to subcutaneous abdominal fat, but not to visceral (omental) fat. Indeed, aromatase activity in omental fat is only one-tenth of the activity in gluteal fat. Estrogens in males play an important role in the regulation of the gonadotropin feedback, several brain functions, bone maturation, regulation of bone resorption and in lipid metabolism. Moreover, they affect skin metabolism and are an important factor determining sex interest in man.

Adrenal Glands↗

PubMed2001

Association of the type I collagen alpha1 Sp1 polymorphism, bone density and upper limb muscle strength in community-dwelling elderly men.

A polymorphic binding site of the Sp1 transcription factor in the gene encoding the alpha1 chain of type I collagen is associated with bone mineral density (BMD) and, independently, with fracture risk in postmenopausal women. The aim of this study is to examine whether in community-dwelling men over age 70 years, the COL1A1 Sp1 polymorphism is associated with BMD (by dual-energy X-ray absorptiometry) and/or with bone turnover and muscle strength--factors related to both BMD and fracture risk. The COL1A1 Sp1 genotype (SS, Ss and ss) was determined using polymerase chain reaction and MscI restriction digestion. Presence of the s allele was significantly associated with lower BMD at the distal forearm (p = 0.03) and different distal radius subregions, with Z-score differences between extreme genotype groups (SS vs ss) ranging from 0.87 (ultradistal radius; p = 0.17) to 1.31 (mid-region of distal radius; p = 0.03). Presence of the s allele was also associated with lower BMD at the hip, with differences between genotypes not approaching statistical significance. There were no differences between genotype groups for any of the assessed markers of bone formation and resorption. Presence of the s allele was associated with lower grip (p = 0.03) and biceps strength (p = 0.04) at the dominant arm, with the difference between extreme genotype groups amounting to 21% and 30%, respectively. In a multivariate analysis, the association between COL1A1 Sp1 polymorphism and forearm BMD Z-score was no longer significant after adjustment for height, percentage lean mass, level of physical activity and upper limb strength (p = 0.18), whereas the genotype-specific difference for grip and biceps strength remained significant after adjustment for age, height and percentage lean mass (p = 0.04 and p= 0.05, respectively). In conclusion, the COL1A1 Sp1 polymorphism is associated with BMD at the forearm and upper limb muscle strength in elderly men, the findings of multivariate analyses suggesting that the genotype-specific differences for BMD might be mediated, at least in part, by differences in muscle strength.

Aged↗

PubMed2001

Inverse association between bone turnover rate and bone mineral density in community-dwelling men >70 years of age: no major role of sex steroid status.

Bone loss is accelerated in elderly men. Little is known about the pathophysiology of senile bone loss or about the role played by relative sex steroid deficiency in the determination of bone turnover in elderly men. In a population-based sample of 283 healthy, ambulatory men, aged 71-86 years, we sought to determine whether lower bone mineral density (BMD; using dual-energy X ray absorptiometry at the hip and the forearm) is associated with higher bone turnover, and we assessed the impact of sex steroid status on bone turnover. Indices of bone formation, serum osteocalcin (s-Oc), and bone-specific alkaline phosphatase (s-bAP) and indices of bone resorption, serum and urinary telopeptide of type I collagen (s-CTx and u-CTx), and urinary free deoxypyridinoline (u-Dpd) were intercorrelated (r = 0.29-0.76, p < 0.001). Bone turnover indices were negatively associated with BMD (r = -0.17 to -0.34, p < 0.01). In univariate analyses, there was a trend toward weak negative associations of bone turnover markers with serum free testosterone (FT), significant only for s-Oc and s-CTx (r = -0.16 and -0.14, p < 0.01), and with serum free estradiol (FE(2)), significant only for u-CTx and s-CTx (r = -0.18 and -0.19; p < 0.01). The lower quartile for FE(2) was associated with higher values of u-CTx (p = 0.003) and s-CTx (p < 0.001). However, in multivariate models, for the individual markers of bone turnover a negative association between estradiol (E(2)) or FE(2) and s-CTx was the only remaining (marginally) significant association (p < 0.05) for the relationship between sex steroids and any of the bone turnover indices assessed. In community-dwelling men age >70 years, bone turnover rate, as determined by biochemical markers, is a significant negative determinant of prevalent BMD. However, the findings do not support the view that relative differences in sex steroid status, as observed among healthy elderly men, have a major impact on bone turnover.

Aged↗

PubMed2001

Evaluation of the simple calculated osteoporosis risk estimation (SCORE) in a sample of white women from Belgium.

Identifying patients at risk of developing an osteoporosis-related fracture will continue to be a challenge. The "gold standard" for osteoporosis diagnosis is bone densitometry. However, economic issues or availability of the technology may prevent its use under a mass screening scenario. A risk assessment instrument, the "simple calculated osteoporosis risk estimation" (SCORE), has been reported to appropriately identify women likely to have low (t score < or = -2 SD) bone mineral density (BMD) and who should be referred for bone densitometry. The aim of our study is to evaluate the discriminatory performance of SCORE in a random sample of postmenopausal white women from Belgium. For this purpose, we gathered medical data on 4035 consecutive patients aged > or = 45 years, either consulting spontaneously or referred for a BMD measurement to an outpatient osteoporosis center located at the University of Liège, Belgium. BMD measurements, using dual-energy X-ray absorptiometry (DXA) technology, were taken at the hip (total and neck) and lumbar spine (L2-4). At the recommended cutoff point of 6, SCORE had a sensitivity of 91.5% to detect low BMD at any of the measured sites, a specificity of 26.5%, a positive predictive value of 52.8%, and a negative predictive value of 77.7%. According to SCORE, 18% of the patients would not be recommended for densitometry. Among these, 10.9% were misclassified as they had osteoporosis (t score < or = -2.5 SD) at one or more of the sites investigated. The negative predictive errors of SCORE, when failing to detect osteoporosis, were only 1% for the total hip, 3.2% for the femoral neck, and 8.8% for the lumbar spine. We conclude that, notwithstanding the high values of sensitivity, SCORE specificity is too low to be useful as a diagnostic tool for screening patients at high risk to later develop osteoporosis. Nevertheless, from a resource allocation perspective, this instrument can be used with relative confidence to exclude patients who do not need a BMD measurement, and would therefore provide an opportunity to realize substantial cost savings in comparison to a mass screening strategy.

Absorptiometry, Photon↗