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Biomedical subjects

Markus J Seibel

Publications and source records attributed to Markus J Seibel.

At least 19 recordsLinked to original sources
PubMed2007

Therapy insight: the risks and benefits of bisphosphonates for the treatment of tumor-induced bone disease.

Bisphosphonates are a valuable class of drugs with potent anti-resorptive actions that make them ideal for skeletal protection in osteoporosis, cancer bone metastasis, multiple myeloma, and Paget's disease of bone. It has become apparent, however, that these drugs also have the potential to cause a number of adverse effects. While these do not limit bisphosphonate use, the incidence of these adverse events can be minimized if appropriate care is taken with their administration, and by maintaining appropriate surveillance and patient care. We review the range of adverse reactions to bisphosphonate therapy with a particular emphasis on the recently identified association between long-term bisphosphonate treatment and osteonecrosis of the jaw. This is a potentially serious side effect seen mostly in patients with multiple myeloma or breast cancer bone metastases who receive intravenous bisphosphonate treatment. While the etiology is uncertain, a strong association with dental pathology and interventions highlights the need for close attention to dental health in this patient group.

Bone Diseases↗
PubMed2006

Inhibition of bone resorption, rather than direct cytotoxicity, mediates the anti-tumour actions of ibandronate and osteoprotegerin in a murine model of breast cancer bone metastasis.

Inhibition of bone resorption either by bisphosphonate (BP) treatment or by blocking RANKL signalling with osteoprotegerin (OPG) has been shown to reduce tumour burden in bone and inhibit bone destruction in murine xenograft models of breast cancer. However, whether the anti-tumour effect of OPG or BP in bone is mediated by inhibition of bone resorption or by direct effects on tumour cells is uncertain. The current study is designed to investigate anti-tumour effects of OPG and ibandronate (IBN), dosed alone or in combination, on tumour growth to determine if there is experimental support for combination treatments and to provide evidence for the presence of direct anti-tumour effects. To this aim, 10 microl (5 x 10(6) cells/ml) of the bone-seeking MDA-MB-231 (Tx-SA) cell line was injected intra-tibially into nude mice. After 10 days, when the tumours were evident radiologically, mice were treated with vehicle, OPG (1 mg/kg/day), ibandronate (IBN) (160 microg/kg/day) or IBN and OPG at the same doses (IBN+OPG) for a week, and the effects of each treatment on lytic lesions, tumour cell growth, cell apoptosis and proliferation were measured by radiography, immunohistochemistry and histomorphometry. Compared to vehicle controls, in vivo treatment with OPG, IBN, or IBN+OPG, each prevented the expansion of osteolytic bone lesions (increase in lytic lesion area day 10 to day 17: OPG -3.2%, IBN 6.6%, IBN+OPG 3.6%, Vehicle 232.5%; p<0.01). Treatment with OPG, IBN or IBN+OPG each produced similar reductions in tumour area relative to vehicle-treated mice (OPG 52%, IBN 54%, IBNp and OPG 48%, p<0.01 vs. vehicle) OPG and IBN alone and in combination each produced a similar increase in cancer cell apoptosis (OPG 330%, IBN 342%, IBN and OPG 347%, p<0.01 vs. vehicle) and a decrease in cancer cell proliferation (OPG 59%, IBN 62%, IBN and OPG 58%, p<0.05 vs. vehicle). Our findings indicate that (i) combined treatment with OPG and a bisphosphonate is not significantly more effective than either agent alone; and that (ii) inhibition of bone resorption, rather than direct anti-tumour action, mediates the effects of these agents on tumour growth in this in vivo model.

Animals↗
PubMed2006

High bone turnover is an independent predictor of mortality in the frail elderly.

UNLABELLED: Osteoporotic fractures are associated with accelerated bone turnover and excess mortality. In a prospective study of 1112 frail subjects (79% female; mean age, 86 years), high bone turnover was an independent predictor of all-cause mortality. This association seemed to be mainly manifested in deaths from cardiovascular causes. INTRODUCTION: Osteoporotic fractures are associated with accelerated bone turnover and excess mortality. In a prospective cohort study of elderly men and women, we assessed whether the rate of bone turnover measured by markers of bone remodeling is a direct predictor of mortality. MATERIALS AND METHODS: We measured serum concentrations of the aminoterminal propeptide of type I collagen (PINP), a marker of bone formation, and of the carboxyterminal telopeptide of type I collagen (CTX-I), a marker of bone resorption, along with serum PTH and 25-hydroxyvitamin D [25(OH)D] levels in 1112 subjects (79% female; mean age, 86 years) living in residential care. Co-morbidity was measured using the Implicit Illness Severity Scale. Fracture data were validated by a radiology report. Mortality and causes of death were ascertained from death certificates. RESULTS: Over a median follow-up of 817 days, 559 (50.3%) subjects died. In univariate analyses, time to death from all causes was significantly (p < 0.01) associated with age (HR = 1.62 per 10 years), male sex (HR = 1.33), immobility (HR = 1.94), co-morbidity (HR = 0.31, mild versus severe), lower weight (HR = 0.83 per 10-kg increase), impaired cognitive function (HR = 2.14, severe versus normal), number of medications (HR = 1.05 each), hip fracture (HR = 2.26), log serum creatinine (HR = 1.67), log PTH (HR = 1.29), CTX-I (HR = 1.70, highest 25% versus lowest 75%), and PINP (HR = 1.46, highest 25% versus lowest 75%). In multivariate analysis adjusting for age, sex, immobility, co-morbidity, weight, cognitive function, number of medications, PTH, and hip fracture status, the highest quartile was significantly more likely to die than the rest for both serum CTX-I (HR = 1.39; 95% CI: 1.14-1.70; p = 0.002) and PINP (HR = 1.25; 95% CI: 1.02-1.52; p = 0.03). For individual causes of death, CTX-I was significantly associated with deaths from cardiac causes (HR = 1.78: 95% CI: 1.27-2.50; p < 0.001). CONCLUSIONS: We conclude that in the frail elderly, high bone turnover is associated with all cause mortality independently of age, sex, health status, serum PTH levels, and hip fracture status. The mechanism of the effect of bone turnover on mortality seems to be mainly manifested in deaths from cardiovascular causes.

Aged↗
PubMed2006

Mechanisms of disease: roles of OPG, RANKL and RANK in the pathophysiology of skeletal metastasis.

The discovery of osteoprotegerin, receptor activator of nuclear factor kappa B (RANK) and RANK ligand as critical molecular determinants of osteoclastogenesis and regulators of bone resorption, has revolutionized our understanding of the processes of normal and pathological bone biology. Altering the relative biological availabilities of these molecules has direct consequences for the regulation of both bone resorption and bone remodeling. Importantly, recent research suggests a pivotal role for these molecules in mediating cancer-induced bone destruction. This review summarizes the current evidence of osteoprotegerin, RANK ligand and RANK involvement in the pathophysiology of skeletal metastasis, and of therapeutic targeting of this process.

Animals↗
PubMed2006

Clinical application of biochemical markers of bone turnover.

With the ageing population in most countries, disorders of bone and mineral metabolism are becoming increasingly relevant to every day clinical practice. Consequently, the interest in, and the need for effective measures to be used in the screening, diagnosis and follow-up of such pathologies have markedly grown. Together with clinical and imaging techniques, biochemical tests play an important role in the assessment and differential diagnosis of metabolic bone disease. In recent years, the isolation and characterisation of cellular and extracellular components of the skeletal matrix have resulted in the development of molecular markers that are considered to reflect either bone formation or bone resorption. These biochemical indices are non-invasive, comparatively inexpensive and, when applied and interpreted correctly, helpful tools in the diagnostic and therapeutic assessment of metabolic bone disease. This review provides an overview of the current evidence regarding the clinical use of biochemical markers of bone remodelling in bone disease, with an emphasis on osteoporosis.

Biomarkers↗
PubMed2006

Serum cathepsin K concentrations reflect osteoclastic activity in women with postmenopausal osteoporosis and patients with Paget's disease.

INTRODUCTION: Cathepsin K, a cysteine protease, plays an essential role in osteoclast-mediated collagen degradation. Recently, an immunoassay to quantify cathepsin K in serum has been developed. We assessed the usefulness of serum cathepsin K as a marker of bone turnover in cross-sectional and longitudinal studies of patients with metabolic bone disease. METHODS: The study cohort consisted of 40 healthy subjects, 21 women with postmenopausal osteoporosis [66.1 +/- 7.9 yrs] and 10 patients with Paget's disease of bone [67.1 +/- 11.6 yrs]. All patients were started on oral or intravenous bisphosphonate treatment and were followed prospectively over 6 months. Circulating cathepsin K levels were determined by a specific sandwich enzyme immunoassay (Biomedica, Vienna, Austria). In addition, serum carboxyterminal cross-linked telopeptide of type I collagen (betaCTX-I) and bone-specific alkaline phosphatase (BALP) were measured for comparison. RESULTS: When compared to healthy subjects, mean serum cathepsin K levels were significantly elevated in women with postmenopausal osteoporosis (3.1 +/- 1.9 vs. 11.3 +/- 13.1 pmol/L, p = 0.01) and in patients with Paget's disease of bone (6.2 +/- 4.4 pmol/L, p = 0.04). In postmenopausal osteoporotic women, both oral and intravenous bisphosphonate treatment resulted in a significant reduction in serum cathepsin K levels (p = 0.03) with most of the effect occurring after one month (mean% change: -33%). In patients with mild Paget's disease, serum cathepsin K levels decreased during bisphosphonate treatment. CONCLUSIONS: Serum concentrations of cathepsin K appear to reflect osteoclastic activity in patients with postmenopausal osteoporosis and Paget's disease of bone and may hold promise as a marker of osteoclast activity.

Aged↗
PubMed2005

Effect of age-related chronic immobility on markers of bone turnover.

UNLABELLED: The effects of acute immobilization on bone turnover are well known, but the effects of chronic hypomobility with aging have not been studied. In a cohort of 1064 frail elderly subjects, immobility was significantly associated with serum PINP but not serum CTx after adjusting for confounders. The effect of immobility may be more marked on bone formation than on bone resorption. INTRODUCTION: Accelerated bone turnover and rapid bone loss caused by acute immobilization is well recognized, but the effects of age-related chronic reduction in mobility on bone turnover have been less well studied. We assessed the associations between bone turnover and measures of mobility in a cohort of elderly subjects. MATERIALS AND METHODS: We measured serum levels of the aminoterminal propeptide of type I collagen (PINP), a marker of bone formation, and serum concentrations of the carboxyterminal telopeptide of type I collagen (CTx), a marker of bone resorption, as well as serum intact PTH, serum 25 hydroxyvitamin D (25OHD), mobility, and static balance in a well-characterized sample of 1064 elderly men and women living in residential aged care facilities. Serum creatinine, phosphate, albumin, and calcium were measured in a randomly selected subgroup of 447 subjects. RESULTS: The subjects were elderly and frail; their mean age was 86.0 years (range, 65-101 years); 69% used a walking aid; and 77% were vitamin D deficient (serum 25OHD level < 39 nM). Both serum PINP and CTx increased with age in both sexes. Elevated PINP or CTx was significantly correlated with high PTH, creatinine, and albumin in both genders, except for albumin in women. Age- and gender-adjusted serum CTx and PINP were significantly higher in those with poorer mobility and those with worse static balance. In multivariate analyses, higher serum PINP but not CTx was associated with poorer mobility and worse static balance. CONCLUSIONS: Our findings suggest that poor mobility contributes to the state of accelerated bone turnover usually seen in the elderly. The effect of chronic relative immobility may be more marked on bone formation than bone resorption.

Age Factors↗
PubMed2005

Perinatal testosterone surge is required for normal adult bone size but not for normal bone remodeling.

Although testosterone (T) has striking effects on mature skeletal size and structure, it is not clear whether this depends exclusively on adult circulating levels of T or whether additional early-life factors also play a role. We have compared the androgen-deficient hypogonadal (hpg) mutant mouse with intact, orchidectomized, and T-treated non-hpg mice to determine relative contributions of adult and perinatal T to bone growth and development. At 3 wk of age, although trabecular and cortical bone structure was normal, bone turnover was significantly altered in hpg male mice; osteoid volume (OV/BV) and osteoblast surface (ObS/BS) were significantly lower and osteoclast surface (OcS/BS) significantly higher in hpg mice compared with age-matched non-hpg mice, pointing to a role for the perinatal T surge in determining bone turnover levels before sexual maturity. At 9 wk of age, the hpg bone phenotype mimicked closely that of age-matched non-hpg mice that had been orchidectomized at 3 wk of age, including low trabecular bone mass and high bone turnover. These bone phenotypes of hpg and orchidectomized non-hpg mice were all prevented by replacement doses of T or dihydrotestosterone (DHT), suggesting that these are determined by adult sex steroid hormones. In contrast, a short bone phenotype that could not be prevented by T or DHT treatment was observed in 9-wk-old hpg mice yet not in intact or castrated non-hpg mice. These data suggest a role for the perinatal T surge in determining adult bone length and confirms that adult circulating T determines adult bone density.

Androgens↗
PubMed2005

Clinical use of markers of bone turnover in metastatic bone disease.

Bone metastases profoundly perturb normal bone remodeling. Biochemical markers of bone turnover have been shown to reflect these tumor-induced changes in bone remodeling and might therefore be useful in the diagnosis and follow-up of patients with malignant bone disease. Most markers of bone turnover, particularly those of bone resorption, are elevated in patients with established bone metastases. While this might indicate a role for bone markers as diagnostic tools in cancer patients, the available evidence does not provide any final conclusions as to the accuracy and validity of the markers presently used in the early diagnosis of bone metastases. Markers of bone resorption respond promptly and profoundly to bisphosphonate and antineoplastic therapy, and this response is associated with a favorable clinical outcome. Most markers, however, have been more useful in groups of patients monitored in clinical studies than in studies of individuals. While this makes them a good tool for drug development, it remains unknown whether the use of bone markers in a routine clinical setting has any defined beneficial effects on overall outcome in cancer patients. In particular, no study has addressed the question of whether patients with bone metastases should be treated according to their rate of bone turnover and what the treatment goals are in this respect. While it is unlikely that bone-turnover markers have sufficient diagnostic or prognostic value when used in isolation, the combination of these markers with other diagnostic techniques might be the way forward to improve the clinical assessment of patients with cancers of the bone.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Biochemical markers of bone turnover: part I: biochemistry and variability.

With the ageing population in most countries, disorders of bone and mineral metabolism are becoming increasingly relevant to every day clinical practice. Consequently, the interest in, and the need for effective measures to be used in the screening, diagnosis and follow-up of such pathologies has markedly grown. Together with clinical and imaging techniques, biochemical tests play an important role in the assessment and differential diagnosis of metabolic bone disease. In recent years, the isolation and characterisation of cellular and extracellular components of the skeletal matrix have resulted in the development of molecular markers that are considered to reflect either bone formation or bone resorption. These biochemical indices are non-invasive, comparatively inexpensive and, when applied and interpreted correctly, helpful tools in the diagnostic and therapeutic assessment of metabolic bone disease. Part I of this article provides an overview of the basic biochemistry of bone markers, and sources of non-specific variability. Part II (to be published in a subsequent issue of this journal) will review the current evidence regarding the clinical use of biochemical markers of bone remodelling in metabolic and metastatic bone disease.

Journal Article↗
PubMed2004

Bone resorption and osteoporotic fractures in elderly men: the dubbo osteoporosis epidemiology study.

UNLABELLED: Among the potential risk factors for fragility fractures, bone turnover is considered an important determinant. In a case-cohort control study of 151 elderly men followed prospectively over 6.3 years, high bone resorption as assessed by S-ICTP was associated with increased risk of osteoporotic fracture, independent of BMD. Combining measurements of BMD and bone turnover may improve fracture prediction in elderly men. INTRODUCTION: Approximately one-third of osteoporotic fractures occur in men. Among the potential risk factors for fragility fractures, bone turnover is considered an important determinant. The association between fracture risk and rates of bone turnover has not been well established in men. We examined this relationship in elderly community-dwelling men. MATERIALS AND METHODS: This case-cohort control study included 50 men with incident low-trauma fractures (cases; age, 72.3 +/- 6.7 years) and 101 men without fracture (controls; age, 70.4 +/- 4.1 years), who have been prospectively followed in the Dubbo Osteoporosis Epidemiology Study for a median of 6.3 years (range, 2-13 years). BMD at the lumbar spine (LSBMD) and at the femoral neck (FNBMD) and markers of bone turnover were measured at baseline. Bone resorption was assessed by measuring nonfasting serum concentrations of the carboxyterminal cross-linked telopeptide of type I collagen (S-ICTP) and of a linear octapeptide derived from the carboxyterminal type I collagen telopeptide (S-CTX). Bone formation was assessed by measuring the serum levels of the aminoterminal propeptide of type I procollagen (S-PINP). RESULTS: Men with subsequent fractures had lower BMD at baseline, both at the femoral neck and the spine, lower dietary calcium intake, and higher S-ICTP levels than age-and weight-matched controls. Smoking habits, S-CTX, and S-PINP did not differ between groups. Based on univariate regression analyses, S-ICTP (relative risk [RR] for 1 SD change: 1.8; 95% CI, 1.4-2.3) and serum creatinine levels (RR, 1.4; 95% CI, 1.1-1.7) were associated with increased risk of fracture. In multivariate regression analyses, S-ICTP (RR, 1.4; 95% CI, 1.0-1.9) and FNBMD (RR, 1.8; 95% CI, 1.4-2.3) remained independent predictors of fracture risk. Men within the highest quartile of S-ICTP had a 2.8-fold (95% CI 1.4-5.4) increased risk of fracture compared with those in the lowest quartile. The incidence of osteoporotic fractures was 10 times higher in men with high S-ICTP and low FNBMD compared with men with low S-ICTP and high FNBMD. Of the fracture risk in the population, 20% was attributable to high S-ICTP and low FNBMD, and S-ICTP contributed 17% to this increased risk. CONCLUSION: High bone resorption is associated with an increased risk of osteoporotic fracture in elderly men, independent of BMD. Combining measurements of BMD and bone turnover, which correlated with fracture in this cohort, could improve fracture risk prediction in elderly men.

Aged↗
PubMed2004

Supplementation with oral vitamin D3 and calcium during winter prevents seasonal bone loss: a randomized controlled open-label prospective trial.

UNLABELLED: Bone metabolism follows a seasonal pattern with high bone turnover and bone loss during the winter. In a randomized, open-label 2-year sequential follow-up study of 55 healthy adults, we found that supplementation with oral vitamin D3 and calcium during winter abolished seasonal changes in calciotropic hormones and markers of bone turnover and led to an increase in BMD. Supplementation with oral vitamin D3 and calcium during the winter months seems to counteract the effects of seasonal changes in vitamin D and thus may be beneficial as a primary prevention strategy for age-related bone loss. INTRODUCTION: Bone metabolism follows a seasonal pattern characterized by high bone turnover and bone loss during winter. We investigated whether wintertime supplementation with oral vitamin D3 and calcium had beneficial effects on the circannual changes in bone turnover and bone mass. MATERIALS AND METHODS: This prospective study comprised an initial observation period of 12 months ("year 1"), followed by an intervention during parts of year 2. Fifty-five healthy subjects living in southwestern Germany (latitude, 49.5 degrees N) were randomized into two groups: 30 subjects were assigned to the treatment group and received oral cholecalciferol (500 IU/day) and calcium (500 mg/day) during the winter months of year 2 (October-April), while 25 subjects assigned to the control group obtained no supplements. Primary endpoints were changes in calciotropic hormones [serum 25(OH)D, 1,25(OH)2D, and parathyroid hormone], markers of bone formation (serum bone-specific alkaline phosphatase) and of bone resorption (urinary pyridinoline and deoxypyridinoline), and changes in lumbar spine and femoral neck BMD. RESULTS: Forty-three subjects completed the study. During year 1, calciotropic hormones, markers of bone turnover, and BMD varied by season in both groups. During the winter months of year 1, bone turnover was significantly accelerated, and lumbar spine and femoral BMD declined by 0.3-0.9%. In year 2, seasonal changes in calciotropic hormones and markers of bone turnover were either reversed or abolished in the intervention group while unchanged in the control cohort. In the subjects receiving oral vitamin D3 and calcium, lumbar and femoral BMD increased significantly (lumbar spine: +0.8%, p = 0.04 versus year 1; femoral neck: +0.1%, p = 0.05 versus year 1), whereas controls continued to lose bone (intervention group versus control group: lumbar spine, p = 0.03; femoral neck, p = 0.05). CONCLUSIONS: Supplementation with oral vitamin D3 and calcium during winter prevents seasonal changes in bone turnover and bone loss in healthy adults. It seems conceivable that annually recurring cycles of low vitamin D and mild secondary hyperparathyroidism during the winter months contributes, at least in part and over many years, to age-related bone loss. Supplementation with low-dose oral vitamin D3 and calcium during winter may be an efficient and inexpensive strategy for the primary prevention of bone loss in northern latitudes.

Absorptiometry, Photon↗
PubMed2004

Analysis of the functional muscle-bone unit of the forearm in pediatric renal transplant recipients.

BACKGROUND: Renal transplantation in children and adolescents is associated with various skeletal complications. The incidence of spontaneous fractures appears to be increased, but the reasons for this are not entirely clear. Our objective was therefore to evaluate macroscopic bone architecture, mass, and strength by peripheral quantitative computed tomography (pQCT), a method that is not influenced by size-related artifacts. In addition, we investigated the muscle-bone relationship in these patients because under physiologic conditions bone strength continually adapts to increasing mechanical loads, that is, muscle force. METHODS: In 55 patients (41 males) aged 15.8 +/- 4.1 years, we evaluated in a cross-sectional study 4.9 +/- 3.6 years after renal grafting bone mass, density, geometry, and strength of the radius, as well as forearm muscle size and strength, using pQCT at the proximal and distal radius, radiography of the second metacarpal shaft and hand dynamometry. Data were compared to a large cohort (N= 350) of healthy children. RESULTS: Muscle mass and force were adequate for body size in pediatric renal transplant recipients. However, the radial bone was characterized by an inadequately thin cortex in relation to muscular force, as shown by a reduced height-adjusted cortical thickness both at the proximal (-0.83 +/- 1.12 SDS) and distal radius (-0.52 +/- 1.69 SDS), the metacarpal shaft (-0.54 +/- 1.35 SDS), and by a reduced relative cortical area (-0.90 +/- 1.13 SDS), while the mineralization of trabecular bone was unaltered. As a consequence of cortical thinning, the Strength-Strain Index that reflects the combined strength of trabecular and cortical bone was reduced in these patients. CONCLUSION: While bone mineral density of the forearm is not decreased in pediatric renal transplant recipients, bone strength in relation to muscular force is reduced. This alteration may contribute to the increased propensity for fractures in these patients.

Adolescent↗
PubMed2004

Recombinant human chorionic gonadotropin but not dihydrotestosterone alone stimulates osteoblastic collagen synthesis in older men with partial age-related androgen deficiency.

Several randomized trials of androgen supplementation in older men have been undertaken. However, the relative contributions of testosterone (T) and estrogens on bone metabolism in aging men are controversial. Within the setting of two double-blind, placebo-controlled studies, we evaluated the effect of dihydrotestosterone (DHT) and recombinant human chorionic gonadotropin (rhCG) on bone turnover in healthy, community-dwelling older men with partial androgen deficiency (total T < or = 15 nmol/liter). In the first study, 35 men (age 68.3 +/- 6.8 yr; baseline T, 13.9 +/- 3.3 nmol/liter) were randomized to receive either daily transdermal DHT (n = 17) or placebo for 3 months. In the second study, 40 men (age 67.4 +/- 5.4 yr; baseline T, 11.4 +/- 2.2 nmol/liter) were randomized to receive either rhCG s.c. (n = 20), two injections weekly, or placebo for 3 months. The following parameters were measured before, monthly during, and 1 month after treatment: serum T, estradiol (E2), and LH; markers of bone formation, serum amino-terminal propeptide of type I procollagen (S-PINP) and osteocalcin; markers of bone resorption, serum carboxyterminal cross-linked telopeptide of type I collagen and urinary deoxypyridinoline. Compared with placebo, treatment with DHT significantly increased serum DHT and suppressed LH and T levels, whereas E2 concentrations and markers of bone turnover did not change. In contrast, rhCG therapy significantly increased both T and E2, with the increases in E2 being supraphysiological. At the same time, rhCG significantly increased S-PINP concentrations with peak levels after 1 month (Delta40%; P = 0.02 compared with placebo). In contrast, serum osteocalcin and carboxyterminal cross-linked telopeptide of type I collagen and urinary deoxypyridinoline levels did not change. The change in S-PINP levels correlated with the change in E2 levels (r = 0.59; P = 0.02) but not with a change in T. We conclude that in older men with partial age-related androgen deficiency, rhCG treatment stimulates osteoblastic collagen formation proportionally to increased E2 concentrations but does not alter markers of mature osteoblastic function or bone resorption. In contrast, treatment with a pure, nonaromatizable androgen (DHT) has no effect on bone turnover despite a 20-fold increase in serum levels. Bone resorption was not accelerated during unchanged (DHT) or increased (rhCG) E2 levels, suggesting that minimal E2 levels are needed to maintain stable resorption, although direct androgen receptor-mediated effects cannot be excluded. If androgen supplementation is required for aging men, aromatizable androgens with sufficient endogenous estrogenic activity may have the most beneficial effects on bone.

Aged↗