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Biomedical subjects

Dirk Vanderschueren

Publications and source records attributed to Dirk Vanderschueren.

At least 19 recordsLinked to original sources
PubMed2007

The diagnosis and treatment of male osteoporosis: Defining, assessing, and preventing skeletal fragility in men.

Male osteoporosis is associated with a significant burden in terms of morbidity, mortality, and economic cost. Despite recent advances in the understanding of the male osteoporotic syndrome, the evaluation and treatment of men suffering from osteoporosis remains a clinical challenge. In men with osteoporosis, it remains particularly critical to exclude underlying pathological causes as these are much more likely to be present than in women. There is increasing evidence that the approaches developed to diagnose and treat the disorder in women may be equally useful in men. The available evidence suggests that the anti-fracture efficacy of treatment with alendronate, risedronate, or teriparatide is similar in both sexes. Additional research is warranted to prospectively address the usefulness of BMD measurements to predict fracture risk, to identify those men who are likely to benefit the most from therapy, and to monitor individual responses to therapy.

Journal Article↗
PubMed2007

Ejaculation latency times and their relationship to penile sensitivity in men with normal sexual function.

PURPOSE: There is a need for objective and validated measurements of ejaculation latency time and penile sensitivity in men with normal sexual function. We determined 1) the normal range and repeatability of ELT in a laboratory vs at home masturbation and intercourse in normal men, 2) the threshold and repeatability of penile sensitivity on 6 penile surface areas measured by 2 vibrometers and 3) whether penile sensitivity correlates with ejaculation latency time. MATERIALS AND METHODS: A total of 58 healthy volunteers between 20 and 40 years old provided ejaculation latency times during 3 procedures and were evaluated with a biothesiometer and SMV-5 vibrometer (Suzuki-Matsuoka, Teknologue, Tokyo, Japan) on 6 penile surface areas. RESULTS: Ejaculation latency time was highest during intercourse (median 8.25 minutes, range 1.32 to 18.31), lower in the laboratory (median 7.22, range 1.37 to 18.79) and lowest during masturbation (median 4.89, range 1.08 to 14.19). The 3 ELT scores were highly reproducible within subjects (ICC 0.88 to 0.93). There was high variability among subjects. Vibrotactile thresholds on 6 penile surface areas were also similar and highly repeatable for the 2 vibrometers (ICC 0.81 to 0.96). However, there was no correlation between penile sensitivity and ELT (R2 less than 8%). CONCLUSIONS: ELT in the laboratory is lower than during intercourse and higher than during masturbation. Vibrometers produce reliable and repeatable penile vibrotactile threshold results. However, penile sensitivity measurements do not correlate with ELT in men with normal sexual function.

Adult↗
PubMed2007

Impact of androgens, growth hormone, and IGF-I on bone and muscle in male mice during puberty.

UNLABELLED: The interaction between androgens and GH/IGF-I was studied in male GHR gene disrupted or GHRKO and WT mice during puberty. Androgens stimulate trabecular and cortical bone modeling and increase muscle mass even in the absence of a functional GHR. GHR activation seems to be the main determinant of radial bone expansion, although GH and androgens are both necessary for optimal stimulation of periosteal growth during puberty. INTRODUCTION: Growth hormone (GH) is considered to be a major regulator of postnatal skeletal growth, whereas androgens are considered to be a key regulator of male periosteal bone expansion. Moreover, both androgens and GH are essential for the increase in muscle mass during male puberty. Deficiency or resistance to either GH or androgens impairs bone modeling and decreases muscle mass. The aim of the study was to investigate androgen action on bone and muscle during puberty in the presence and absence of a functional GH/insulin-like growth factor (IGF)-I axis. MATERIALS AND METHODS: Dihydrotestosterone (DHT) or testosterone (T) were administered to orchidectomized (ORX) male GH receptor gene knockout (GHRKO) and corresponding wildtype (WT) mice during late puberty (6-10 weeks of age). Trabecular and cortical bone modeling, cortical strength, body composition, IGF-I in serum, and its expression in liver, muscle, and bone were studied by histomorphometry, pQCT, DXA, radioimmunoassay and RT-PCR, respectively. RESULTS: GH receptor (GHR) inactivation and low serum IGF-I did not affect trabecular bone modeling, because trabecular BMD, bone volume, number, width, and bone turnover were similar in GHRKO and WT mice. The normal trabecular phenotype in GHRKO mice was paralleled by a normal expression of skeletal IGF-I mRNA. ORX decreased trabecular bone volume significantly and to a similar extent in GHRKO and WT mice, whereas DHT and T administration fully prevented trabecular bone loss. Moreover, DHT and T stimulated periosteal bone formation, not only in WT (+100% and +100%, respectively, versus ORX + vehicle [V]; p < 0.05), but also in GHRKO mice (+58% and +89%, respectively, versus ORX + V; p < 0.05), initially characterized by very low periosteal growth. This stimulatory action on periosteal bone resulted in an increase in cortical thickness and occurred without any treatment effect on serum IGF-I or skeletal IGF-I expression. GHRKO mice also had reduced lean body mass and quadriceps muscle weight, along with significantly decreased IGF-I mRNA expression in quadriceps muscle. DHT and T equally stimulated muscle mass in GHRKO and WT mice, without any effect on muscle IGF-I expression. CONCLUSIONS: Androgens stimulate trabecular and cortical bone modeling and increase muscle weight independently from either systemic or local IGF-I production. GHR activation seems to be the main determinant of radial bone expansion, although GHR signaling and androgens are both necessary for optimal stimulation of periosteal growth during puberty.

Androgens↗
PubMed2006

Relative impact of androgen and estrogen receptor activation in the effects of androgens on trabecular and cortical bone in growing male mice: a study in the androgen receptor knockout mouse model.

UNLABELLED: The relative importance of AR and ER activation has been studied in pubertal male AR knockout and WT mice after orchidectomy and androgen replacement therapy, either with or without an aromatase inhibitor. AR activation dominates normal trabecular bone development and cortical bone modeling in male mice. Moreover, optimal periosteal bone expansion is only observed in the presence of both AR and ER activation. INTRODUCTION: Androgen receptor (AR)-mediated androgen action has traditionally been considered a key determinant of male skeletal growth. Increasing evidence, however, suggests that estrogens are also essential for normal male bone growth. Therefore, the relative importance of AR-mediated and estrogen receptor (ER)-mediated androgen action after aromatization remains to be clarified. MATERIALS AND METHODS: Trabecular and cortical bone was studied in intact or orchidectomized pubertal AR knockout (ARKO) and male wildtype (WT) mice, with or without replacement therapy (3-8 weeks of age). Nonaromatizable (dihydrotestosterone [DHT]) and aromatizable (testosterone [T]) androgens and T plus an aromatase inhibitor (anastrazole) were administered to orchidectomized ARKO and WT mice. Trabecular and cortical bone modeling were evaluated by static and dynamic histomorphometry, respectively. RESULTS: AR inactivation or orchidectomy induced a similar degree of trabecular bone loss (-68% and -71%, respectively). Both DHT and T prevented orchidectomy-induced bone loss in WT mice but not in ARKO mice. Administration of an aromatase inhibitor did not affect T action on trabecular bone. AR inactivation and orchidectomy had similar negative effects on cortical thickness (-13% and -8%, respectively) and periosteal bone formation (-50% and -26%, respectively). In orchidectomized WT mice, both DHT and T were found to stimulate periosteal bone formation and, as a result, to increase cortical thickness. In contrast, the periosteum of ARKO mice remained unresponsive to either DHT or T. Interestingly, administration of an aromatase inhibitor partly reduced T action on periosteal bone formation in orchidectomized WT mice (-34% versus orchidectomized WT mice on T), but not in ARKO mice. This effect was associated with a significant decrease in serum IGF-I (-21% versus orchidectomized WT mice on T). CONCLUSIONS: These findings suggest a major role for AR activation in normal development of trabecular bone and periosteal bone growth in male mice. Moreover, optimal stimulation of periosteal growth is only obtained in the presence of both AR and ER activation.

Androgens↗
PubMed2006

Dihydrotestosterone treatment results in obesity and altered lipid metabolism in orchidectomized mice.

OBJECTIVE: To determine the role of androgen receptor (AR) activation for adipose tissue metabolism. Sex steroids are important regulators of adipose tissue metabolism in men. Androgens may regulate the adipose tissue metabolism in men either directly by stimulation of the AR or indirectly by aromatization of androgens into estrogens and, thereafter, by stimulation of the estrogen receptors. Previous studies have shown that estrogen receptor alpha stimulation results in reduced fat mass in men. RESEARCH METHODS AND PROCEDURES: Orchidectomized mice were treated with the non-aromatizable androgen 5alpha-dihydrotestosterone (DHT), 17beta-estradiol, or vehicle. Vo(2), Vco(2), resting metabolic rate, locomotor activity, and food consumption were measured. Furthermore, changes in hepatic gene expression were analyzed. RESULTS: DHT treatment resulted in obesity, associated with reduced energy expenditure and fat oxidation. In contrast, DHT did not affect food consumption or locomotor activity. Furthermore, DHT treatment resulted in increased high-density lipoprotein-cholesterol and triglyceride levels associated with markedly decreased 7alpha-hydroxylase gene expression, indicating decreased bile acid production. DISCUSSION: We showed that AR activation results in obesity and altered lipid metabolism in orchidectomized mice. One may speculate that AR antagonists might be useful in the treatment of obesity in men.

Adiposity↗
PubMed2006

Optimizing the benefits of bisphosphonates in osteoporosis : the importance of appropriate calcium intake.

Osteoporosis is a major cause of morbidity, mortality, and healthcare costs. The socioeconomic burden of osteoporosis is likely to increase dramatically if improvements in prevention are not made. Calcium supplementation effectively reduces the rate of bone loss in postmenopausal women, yet most women do not achieve an adequate calcium intake. In fact, use of calcium supplementation appears to have declined as the more effective antiresorptive therapies, such as bisphosphonates, have become available. Among patients prescribed bisphosphonates, calcium intake is often insufficient, despite the fact that adequate calcium intake may be necessary to gain the maximum benefits from antiresorptive therapy. In addition, because calcium interferes with bisphosphonate absorption, incorrect use of calcium may limit the efficacy of bisphosphonate therapy. This underscores the need for new initiatives to reduce the confusion surrounding appropriate calcium use during antiresorptive therapy. Co-packaging of bisphosphonates with calcium supplements is one strategy to help ensure that patients taking bisphosphonates not only achieve adequate calcium intake but also gain the maximum benefit from bisphosphonate therapy.

Calcium, Dietary↗
PubMed2005

Clinical Review: Sex steroids and the periosteum--reconsidering the roles of androgens and estrogens in periosteal expansion.

CONTEXT: Traditionally, differences in periosteal bone formation between men and women have been assumed to reflect two diverging endocrine effects: stimulatory effects of androgens in men and inhibitory effects of estrogens in women. In line with this concept, it is tempting to speculate that men experience more periosteal bone expansion than women because they are exposed to more endogenous androgens and less estradiol. However, recent data challenge this traditional concept. EVIDENCE ACQUISITION: A PubMed search was conducted for relevant most recent findings in both humans and animals in the context of an intriguing observation of ongoing periosteal expansion after estrogen treatment in an aromatase-deficient boy. EVIDENCE SYNTHESIS: Human experiments of nature have provided evidence that androgens and estrogens are both required for the process of pubertal periosteal bone expansion typically associated with the male bone phenotype. Androgens alone appear insufficient to drive male periosteal bone formation. In both sexes, androgens may stimulate periosteal bone formation, but low levels of estrogen may increase the mechanical sensitivity of the periosteum. Higher concentrations of endogenous estrogen, however, inhibit periosteal bone apposition and/or its interaction with mechanical loading. This biphasic action of estrogen on the periosteum may result from a direct effect on its receptor, either alpha or beta, but may also depend on changes in serum IGF-I. CONCLUSIONS: Simple concepts of the roles of sex steroids in periosteal apposition have to be reconsidered in the context of these recent findings.

Androgens↗
PubMed2005

Growth without growth hormone receptor: estradiol is a major growth hormone-independent regulator of hepatic IGF-I synthesis.

UNLABELLED: The role of estrogens in the regulation of pubertal growth independently of GH and its receptor was studied in male mice with disrupted GHRKO. E(2) rescued skeletal growth rates in GHRKO associated with an increase in hepatic and serum IGF-I. These data show that E(2) rescues pubertal growth during GH resistance through a novel mechanism of GHR-independent stimulation of hepatic IGF-I production. INTRODUCTION: Growth hormone (GH) and estrogen play a pivotal role in pubertal growth and bone mineral acquisition. Estrogens can affect GH secretion and thereby provide a GH-dependent mechanism for their effects on skeletal growth. It is presently unclear if or to what extent estrogens are able to regulate pubertal growth and bone mineral accrual independently of GH and its receptor. MATERIALS AND METHODS: Estradiol (E(2); 0.03 mug/day by subcutaneous silastic implants) was administered to orchidectomized (ORX) male mice with disrupted GHR (GHRKO) and corresponding WTs during late puberty (6-10 weeks). Longitudinal and radial bone growth, IGF-I in serum and its expression in liver, muscle, and bone, and liver gene expression were studied by histomorphometry, RIA, RT-PCR, microarrays, and Western blotting, respectively. RESULTS: E(2) stimulated not only longitudinal (femur length and growth plate thickness) and radial growth (cortical thickness and periosteal perimeter), but also rescued longitudinal and periosteal growth rates in ORX GHRKO, whereas no significant changes occurred in WT. E(2) thereby upregulated serum IGF-I and liver IGF-I synthesis (+21% and +52%, respectively) in ORX GHRKO, whereas IGF-I synthesis in femur or muscle was unaffected. Study of the underlying mechanism of the stimulation of hepatic IGF-I expression showed that E(2) restored downregulated receptor signaling systems, such as the estrogen receptor alpha and the prolactin receptor. E(2) thereby recovered the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway as evidenced by a significantly increased activation of the transcription factor STAT5 in ORX GHRKO. CONCLUSIONS: Our data show a stimulation of skeletal growth through upregulation of hepatic IGF-I by a hormone other than GH. E(2) rescues pubertal skeletal growth during GH resistance through a novel mechanism of GHR-independent stimulation of IGF-I synthesis in the liver.

Animals↗
PubMed2005

Bone and muscle protective potential of the prostate-sparing synthetic androgen 7alpha-methyl-19-nortestosterone: evidence from the aged orchidectomized male rat model.

This study reports the preclinical evaluation of the bone and muscle protective potential of the synthetic androgen 7alpha-methyl-19-nortestosterone (MENTtrade mark), as assessed in the aged orchidectomized rat model. Aged (13-month-old) orchidectomized Wistar rats were treated with different doses of MENT (4, 12 or 36 microg/day) subcutaneously for 16 weeks via mini-osmotic pumps. Analysis of the effects of androgen deficiency versus MENT replacement was performed using quantitative computed tomography (pQCT), dual energy X-ray absorptiometry (DEXA) and biochemical markers of bone turnover. At the end of the study period, prostate weight in orchidectomized rats treated with low- (4 microg/day) or mid-dose (12 mug/day) MENT remained significantly lower compared to the sham-operated animals (-47% and -25%, respectively). High-dose MENT (36 microg/day), on the other hand, induced prostate hypertrophy (+21% versus sham). Low-, mid- and high-dose MENT were found to be effective in suppressing the acceleration of bone remodeling following orchidectomy, as assessed by osteocalcin and deoxypyridinoline. In addition, low-, mid- and high-dose were able to prevent the orchidectomy-induced bone loss, as evaluated by DEXA at the femur and total-body and by pQCT at the femur. Compared to sham-operated animals, the low- and mid-dose MENT groups showed no decline in lean body mass and no muscle atrophy (as measured by m. quadriceps weight) at 16 weeks, whereas high-dose MENT was associated with a significant decline in lean body mass (-8.5% versus sham) and quadriceps weight (-10.6%). We conclude that, in the aged orchidectomized rat model, low- and mid-doses of the synthetic androgen MENT have bone and muscle protective effects and do not induce prostate hypertrophy. The bone protective action of high-dose MENT, however, occurs at the expense of muscle wasting and prostate hypertrophy. Our findings support the need for human studies to explore the potential of MENT as an option for androgen replacement in aging men.

Absorptiometry, Photon↗
PubMed2005

Reversing sex steroid deficiency and optimizing skeletal development in the adolescent with gonadal failure.

During puberty, the acquisition of skeletal mass and areal bone mineral density (BMD) mainly reflects an increase in bone size (length and perimeters) and not true volumetric BMD. Sexual dimorphism in bone mass and areal BMD is also explained by differences in bone size (longer and wider bones in males) and not by differences in volumetric BMD. Androgens stimulate skeletal growth by activation of the androgen receptor, whereas estrogens (following aromatization of androgens and stimulation of estrogen receptors) have a biphasic effect on skeletal growth during puberty. Recent evidence from clinical cases has shown that many of the growth-promoting effects of the sex steroids are mediated through estrogens rather than androgens. In addition, skeletal maturation and epiphyseal fusion are also estrogen-dependent in both sexes. Nevertheless, independent actions of androgens in these processes also occur. Both sex steroids maintain volumetric BMD during puberty. Androgens interact with the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis neonatally, resulting in a sexual dimorphic GH pattern during puberty, whereas estrogens stimulate GH and hereby IGF-I in both sexes. Hypogonadism in adolescents impairs not only bone size but also maintenance of volumetric BMD, hereby severely reducing peak areal BMD. Delayed puberty in boys and Turner's syndrome in women impair both bone length and size, reducing areal BMD. Whether volumetric BMD is also reduced and whether fracture risk is increased in these conditions remains controversial. Replacing sex steroids according to a biphasic pattern (starting at low doses and ending at high-normal doses) seems the safest approach to reach targeted height and to optimize bone development.

Adolescent↗
PubMed2004

Evidence from data searches and life-table analyses for gender-related differences in absolute risk of hip fracture after Colles' or spine fracture: Colles' fracture as an early and sensitive marker of skeletal fragility in white men.

UNLABELLED: Based on data searches and life-table analyses, we determined the long-term (remaining lifetime) and short-term (10- and 5-year) absolute risks of hip fracture after sustaining a Colles' or spine fracture and searched for potential gender-related differences. In aging men, Colles' fractures carry a higher absolute risk for hip fracture than spinal fractures in contrast to women. These findings support the concept that forearm fracture is an early and sensitive marker of male skeletal fragility. INTRODUCTION: Colles' fracture occurrence has been largely ignored in public health approaches to identify target populations at risk for hip fracture. The aim of this study was to estimate the long-term and short-term absolute risks of hip fracture after sustaining a Colles' or spine fracture and to search for potential gender-related differences in the relationship between fracture history and future fracture risk. MATERIALS AND METHODS: To determine the long-term (remaining lifetime) and short-term (10- and 5-year) absolute risks of hip fracture, we applied life-table methods using U.S. age- and sex-specific hip fracture incidence rates, U.S. age-specific mortality rates for white women and men, pooled hazard ratios for mortality after Colles' and spine fracture, and pooled relative risks for hip fracture after Colles' and spine fracture, estimated from cohort studies by standard meta-analytic methods. RESULTS: Our results indicate that the estimated remaining lifetime risks are dependent on age in both genders. In women, remaining lifetime risks increase until the age of 80 years, when they start to decline because of the competing probabilities of fracture and death. The same pattern is found in men until the age of 85 years, the increment in lifetime risk being even more pronounced. As expected, the risk of sustaining a hip fracture was found to be higher in postmenopausal women with a previous spine fracture compared with those with a history of Colles' fracture. In men, on the other hand, the prospective association between fracture history and subsequent hip fracture risk seemed to be strongest for Colles' fracture. At the age of 50, for example, the remaining lifetime risk was 13% in women with a previous Colles' fracture compared with 15% in the context of a previous spine fracture and 9% among women of the general population. In men at the age of 50 years, the corresponding risk estimates were 8%, 6%, and 3%, respectively. Similar trends were observed when calculating 5- and 10-year risks. CONCLUSIONS: In aging men, Colles' fractures carry a higher absolute risk for hip fracture than spinal fractures in contrast to women. These findings support the concept that forearm fracture is an early and sensitive marker of male skeletal fragility. The gender-related differences reported in this analysis should be taken into account when designing screening and treatment strategies for prevention of hip fracture in men.

Age Factors↗
PubMed2004

Additive protective effects of estrogen and androgen treatment on trabecular bone in ovariectomized rats.

UNLABELLED: Both ER and AR activation regulates trabecular bone mass. We show that combined estrogen and androgen treatment results in additive protection of trabecular bone in OVX rats. This may in part be attributable to the effect of AR activation to attenuate the inhibitory effect of ER activation on bone formation. INTRODUCTION: Sex steroids are important regulators of trabecular bone mass. Both estrogen receptor (ER) and androgen receptor (AR) activation results in increased trabecular bone mass. The aim of this study was to investigate if combined estrogen and androgen treatment might be beneficial in the treatment of trabecular bone loss. MATERIALS AND METHODS: Twelve-week-old female rats were ovariectomized (OVX) and treated with vehicle (V), 17beta-estradiol (E2; ER activation), dihydrotestosterone (DHT; AR activation), or the combination (E2 + DHT) for 6 weeks. The skeletal phenotype was analyzed by pQCT, microCT, histomorphometry of growth plates, and serum levels of biochemical bone markers. RESULTS: Both E2 (+121% over V) and DHT (+34%) preserved the trabecular volumetric BMD (tvBMD) in OVX rats. The effect of E2 and DHT on tvBMD was additive, resulting in a 182% increase over V in the rats given E2 + DHT. MicroCT analyses of the trabecular bone microstructure revealed that the effect of E2 and DHT was additive on the number of trabeculae. E2 treatment reduced serum markers of both bone resorption (collagen C-terminal telopeptide) and bone formation (osteocalcin), indicating reduced bone turnover. Addition of DHT to E2 treatment did not modulate the effects of E2 on the marker of bone resorption, whereas it attenuated the inhibitory effect of E2 on the bone formation marker, which might explain the additive protective effect of E2 and DHT on trabecular bone mass. In contrast, DHT partially counteracted the suppressive effect of E2 on longitudinal bone growth and the E2-induced alterations in growth plate morphology. CONCLUSIONS: These findings show that combined estrogen and androgen treatment results in additive protective effects on trabecular bone in OVX rats. Our data suggest that a combined treatment with selective ER and AR modulators might be beneficial in the treatment of osteoporosis.

Androgens↗
PubMed2004

Identifying postmenopausal women with osteoporosis by calcaneal ultrasound, metacarpal digital X-ray radiogrammetry and phalangeal radiographic absorptiometry: a comparative study.

Identifying women with osteoporosis remains a clinical challenge, as it may not be feasible or cost-effective to recommend dual-energy X-ray absorptiometry (DXA) for all postmenopausal women. In this regard, quantitative ultrasound (QUS) has emerged as an attractive screening tool because of the (relatively) low cost and because QUS and DXA-assessed BMD appear to be equally predictive of future (hip) fracture risk. The objective of this study was to compare the ability of calcaneal QUS to identify osteoporosis with two alternative potential screening methods: digital X-ray radiogrammetry (DXR) and radiographic absorptiometry (RA). We enrolled a total of 221 postmenopausal community-dwelling Caucasian women aged 50-75 years. Bone mineral density (BMD) was measured at the lumbar spine and the total hip regions using DXA. Calcaneal ultrasound attenuation and velocity were assessed using QUS and metacarpal and phalangeal bone density were estimated by the use of DXR and RA, respectively. Receiver operating characteristic (ROC) curves were constructed by calculating the specificity and sensitivity of QUS, DXR, and RA at different cut-point values in discriminating osteoporosis, as defined by a T-score below -2.5 at the spine or hip using DXA, and the areas under the curves (AUCs) were computed. The sensitivity for identifying women with osteoporosis was 67.6% [95% confidence interval (CI), 50.2-82.0%] using QUS and was 76.9% (95% CI, 60.7-88.8%) and 82.9% (95% CI, 67.9-92.8%), respectively, using DXR and RA. The negative predictive value (NPV, the proportion of patients with a negative test who have no osteoporosis) was 90% for QUS, compared with an NPV of 94% for both DXR and RA. These data suggest that metacarpal DXR and phalangeal RA may be as effective as calcaneal QUS for targeting DXA testing in high-risk postmenopausal women.

Absorptiometry, Photon↗
PubMed2004

Role of the androgen receptor in skeletal homeostasis: the androgen-resistant testicular feminized male mouse model.

UNLABELLED: The role of androgen receptor-mediated androgen action on bone was investigated in testicular feminized male (Tfm) mice. Cortical bone was found to be unresponsive to testosterone (T) in orchidectomized Tfm mice, whereas cortical thickness as well as trabecular BMD and structure were fully maintained by T in the corresponding Tabby control mice. These data show an essential role for androgen receptor-mediated androgen action in periosteal bone formation. INTRODUCTION: Androgens can affect the male skeleton both directly-through activation of the androgen receptor (AR)-and indirectly-through stimulation of estrogen receptors after aromatization. We assessed the importance of AR-mediated androgen action on bone in a mouse model of androgen resistance. MATERIALS AND METHODS: Eight-week-old androgen-resistant testicular feminized male (Tfm) and Tabby control mice were orchidectomized (ORX) and treated for 4 weeks with a slow-release testosterone (T) pellet (delivering 167 microg/day) or a placebo pellet. A comprehensive analysis of the skeletal effects of androgen deficiency and replacement was performed using histomorphometry, QCT, and biochemical assessment of bone turnover. RESULTS: As expected, T increased trabecular BMD, volume, number, and width in ORX Tabby mice. In ORX Tfm mice, however, T had less effect on trabecular BMD and no effect on trabecular bone structure. T action on trabecular bone was associated with opposite changes in bone turnover: trabecular and endocortical bone turnover and serum levels of osteocalcin were all reduced by T in ORX Tabby mice, but not in ORX Tfm mice. T also increased cortical thickness (+16%), area, and density in ORX Tabby mice, but not in Tfm mice, resulting in greater bone strength in the Tabby control strain. The positive effects of T on cortical bone reflected a stimulatory effect on periosteal bone formation (+137%), which was again absent in Tfm mice. CONCLUSIONS: These data show that, in male mice, AR-mediated T action is essential for periosteal bone formation and contributes to trabecular bone maintenance.

Androgen-Insensitivity Syndrome↗
PubMed2004

Androgens and bone.

Loss of estrogens or androgens increases the rate of bone remodeling by removing restraining effects on osteoblastogenesis and osteoclastogenesis, and also causes a focal imbalance between resorption and formation by prolonging the lifespan of osteoclasts and shortening the lifespan of osteoblasts. Conversely, androgens, as well as estrogens, maintain cancellous bone mass and integrity, regardless of age or sex. Although androgens, via the androgen receptor (AR), and estrogens, via the estrogen receptors (ERs), can exert these effects, their relative contribution remains uncertain. Recent studies suggest that androgen action on cancellous bone depends on (local) aromatization of androgens into estrogens. However, at least in rodents, androgen action on cancellous bone can be directly mediated via AR activation, even in the absence of ERs. Androgens also increase cortical bone size via stimulation of both longitudinal and radial growth. First, androgens, like estrogens, have a biphasic effect on endochondral bone formation: at the start of puberty, sex steroids stimulate endochondral bone formation, whereas they induce epiphyseal closure at the end of puberty. Androgen action on the growth plate is, however, clearly mediated via aromatization in estrogens and interaction with ERalpha. Androgens increase radial growth, whereas estrogens decrease periosteal bone formation. This effect of androgens may be important because bone strength in males seems to be determined by relatively higher periosteal bone formation and, therefore, greater bone dimensions, relative to muscle mass at older age. Experiments in mice again suggest that both the AR and ERalpha pathways are involved in androgen action on radial bone growth. ERbeta may mediate growth-limiting effects of estrogens in the female but does not seem to be involved in the regulation of bone size in males. In conclusion, androgens may protect men against osteoporosis via maintenance of cancellous bone mass and expansion of cortical bone. Such androgen action on bone is mediated by the AR and ERalpha.

Androgens↗
PubMed2004

Estrogens are essential for male pubertal periosteal bone expansion.

The skeletal response to estrogen therapy was studied in a 17-yr-old boy with congenital aromatase deficiency. As expected, estrogen therapy (1 mg estradiol valeriate/d from age 17 until 20 yr) normalized total and free testosterone and reduced the rate of bone remodeling. Dual-energy x-ray absorptiometry-assessed areal bone mineral density (BMD) of the lumbar spine and femoral neck increased significantly (by 23% and 14%, respectively), but peripheral quantitative computed tomography at the ultradistal radius revealed no gain of either trabecular or cortical volumetric BMD. The increase in areal BMD was thus driven by an increase in bone size. Indeed, longitudinal bone growth (height, +8.5%) and especially cross-sectional area of the radius (+46%) and cortical thickness (+12%), as measured by peripheral quantitative computed tomography, increased markedly during estrogen treatment. These findings demonstrate that androgens alone are insufficient, whereas estrogens are essential for the process of pubertal periosteal bone expansion typically associated with the male bone phenotype.

Adolescent↗
PubMed2003

Effect of 6-month whole body vibration training on hip density, muscle strength, and postural control in postmenopausal women: a randomized controlled pilot study.

UNLABELLED: High-frequency mechanical strain seems to stimulate bone strength in animals. In this randomized controlled trial, hip BMD was measured in postmenopausal women after a 24-week whole body vibration (WBV) training program. Vibration training significantly increased BMD of the hip. These findings suggest that WBV training might be useful in the prevention of osteoporosis. INTRODUCTION: High-frequency mechanical strain has been shown to stimulate bone strength in different animal models. However, the effects of vibration exercise on the human skeleton have rarely been studied. Particularly in postmenopausal women-who are most at risk of developing osteoporosis-randomized controlled data on the safety and efficacy of vibration loading are lacking. The aim of this randomized controlled trial was to assess the musculoskeletal effects of high-frequency loading by means of whole body vibration (WBV) in postmenopausal women. MATERIALS AND METHODS: Seventy volunteers (age, 58-74 years) were randomly assigned to a whole body vibration training group (WBV, n = 25), a resistance training group (RES, n = 22), or a control group (CON, n = 23). The WBV group and the RES group trained three times weekly for 24 weeks. The WBV group performed static and dynamic knee-extensor exercises on a vibration platform (35-40 Hz, 2.28-5.09g), which mechanically loaded the bone and evoked reflexive muscle contractions. The RES group trained knee extensors by dynamic leg press and leg extension exercises, increasing from low (20 RM) to high (8 RM) resistance. The CON group did not participate in any training. Hip bone density was measured using DXA at baseline and after the 6-month intervention. Isometric and dynamic strength were measured by means of a motor-driven dynamometer. Data were analyzed by means of repeated measures ANOVA. RESULTS: No vibration-related side effects were observed. Vibration training improved isometric and dynamic muscle strength (+15% and + 16%, respectively; p < 0.01) and also significantly increased BMD of the hip (+0.93%, p < 0.05). No changes in hip BMD were observed in women participating in resistance training or age-matched controls (-0.60% and -0.62%, respectively; not significant). Serum markers of bone turnover did not change in any of the groups. CONCLUSION: These findings suggest that WBV training may be a feasible and effective way to modify well-recognized risk factors for falls and fractures in older women and support the need for further human studies.

Aged↗