Effect of testosterone on bone in hypogonadal males.

Bone mineral content (BMC) and testosterone levels were evaluated and compared in 10 hypogonadal males and 10 normal, age-matched controls. In 6 of the subjects an investigation was also carried out into the effects of testosterone administration on lumbar BMC, calcitonin (CT) response to hypercalcaemia, osteocalcin (BGP) and the fasting urinary calcium/creatinine and hydroxyproline/creatinine ratios. Our results confirm that male hypogonadism is characterized by a low BMC and that testosterone administration is able to improve this parameter and to increase both basal BGP and CT response to hypercalcaemia. Testosterone therefore probably acts on bone tissue through both a direct action on osteoblast cells and an improvement in CT secretion.     

Low bone mass in hypogonadal males. Effect of testosterone substitution therapy, a densitometric study.

Sixteen (16) male patients who were suffering from hypogonadism but who were free from bone symptoms were recruited from the Andrology Clinic. Their bone mineral density (BMD) was assessed by single photon absorptiometry in the non-dominant radius, at both the distal radius (DR) (27% trabecular bone) and the midshaft radius (MR) (90% cortical bone). Measurements were carried out before and during testosterone substitution therapy. BMD was found to be lower in the subjects than in the controls, to a similar extent at both the DR (0.47 +/- 0.02 g/cm2, i.e. 83.1 +/- 4.3% of the value in the controls, or Z score -1.42 +/- 0.39; P less than 0.01) and the MR (0.68 +/- 0.02 g/cm2, i.e. 87.8 +/- 2.4% of the value in the controls, or Z score -1.49 +/- 0.33; P less than 0.01). There was no correlation between testosterone levels and BMD at either the DR or the MR at the beginning of the study. Following testosterone substitution therapy, bone mineral content (BMC) increased significantly at the DR (+5.9 +/- 1.4% per year; P less than 0.01) and at the MR (+1.1 +/- 0.9% per year; P less than 0.01). If the study is limited to the subjects who had achieved full bone age maturity before the start of therapy, the bone gain remains significant only at the DR, a site with a sizeable proportion of trabecular bone.     

Effect of estrogen on bone resorption and inflammation in the temporomandibular joint cellular elements

Several epidemiological studies have reported that temporomandibular disorder is more prevalent in women, which suggests the involvement of sex hormones, such as estrogen, in the pathogenesis of this disease. PCR amplification and Western blotting were employed to target the expression of estrogen receptors (ERs) in human fibroblast-like synovial and ATDC5 cells. The effect of estrogen was investigated through the expression of RANKL, osteoprotegerin (OPG), M-CSF/CSF-1 and c-fms. We showed expression of M-CSF/ CSF-1 and c-fms, with time-dependent increase in both after the addition of estrogen. Based on previous studies reporting that M-CSF/CSF-1 regulates the proliferation and differentiation of hemopoietic progenitor cells into mature macrophages, we put forward a new hypothesis based on the increased inflammation and tendency of females to suffer more from temporomandibular disorder (TMD) in the presence of external exacerbating factors. Detection of RANKL and OPG in ATDC5 and expression of both in HFLS was confirmed with complete disappearance of the RANKL band, and marked increase in the expression of OPG after 1 h from the addition of estrogen.     

The effects of acute exercise on serum adiponectin and resistin levels and their relation to insulin sensitivity in overweight males

The purpose of this study was to investigate the effects of a submaximal aerobic exercise bout on adiponectin and resistin levels as well as insulin sensitivity, until 48 h post-exercise in healthy overweight males. Nine subjects performed an exercise bout at an intensity corresponding to approximately 65% of their maximal oxygen consumption for 45 min. Adiponectin, resistin, cortisol, insulin, glucose and insulin sensitivity were measured prior to exercise, immediately after exercise as well as 24 and 48 h after exercise. Data were analyzed using repeated measures ANOVA while Pearson’s correlations were performed to identify possible relationship among the assessed variables. There were no significant differences for adiponectin (μg ml⁻¹) [pre, 3.61(0.73); post, 3.15(0.43); 24 h, 3.15(0.81); 48 h, 3.37(0.76)] or resistin (ng ml⁻¹) [pre, 0.19(0.03); post, 0.13(0.03); 24 h, 0.23(0.04); 48 h, 0.23(0.03)] across time. Insulin sensitivity increased and insulin concentration decreased significantly only immediately after exercise. Furthermore, no significant correlations were observed among the variables assessed except for the expected between insulin level and insulin sensitivity. These results indicate that a submaximal aerobic workout does not result in significant changes in adiponectin and resistin up to 48 h post-exercise. Furthermore, it appears that adiponectin or resistin is not associated with insulin sensitivity.     

Influence of estrogen replacement therapy on plasma lipid peroxidation.

OBJECTIVE: To observe whether any relationship exists between the concentration of plasma estradiol (E2) and the plasma concentrations of malondialdehyde (MDA) or whether a relationship exists between the concentration of plasma E2 and the activity of the erythrocyte enzymes, superoxide dismutase (SOD) and catalase, in ovariectomized female Wistar rats (treated and untreated with E2). DESIGN: We used 40 ovariectomized Wistar rats randomly assigned to four groups. The first group was allowed to evolve freely with no treatment. A gel containing 17beta-estradiol was administered transdermally to the other three groups at doses of 4, 8, and 16 microg/day, respectively. After 15 days of treatment, blood samples were obtained from the four groups. The concentrations of plasma MDA and E2 and the activities of erythrocyte catalase and SOD were determined. RESULTS: There were significant correlations between the MDA levels and the logarithm (base 10) of the plasma E2 concentrations in both linear (p = 0.00093) and quadratic (p = 0.000001) regression analyses. No relationship was found between the E2 concentrations and the catalase and SOD activities. CONCLUSIONS: There was a clear relationship between the plasma levels of MDA and the logarithm of the plasma E2 concentrations, which was best demonstrated with a quadratic regression. This model may explain the contradictory findings presented by estrogens with respect to their pro-or antioxidant action.     

骨水泥中的硫酸钡对破骨细胞的作用

目的验证骨水泥中的硫酸钡对破骨细胞形成及其生物学活性的影响。方法体外培养外周血单核细胞并加入巨噬细胞克隆集落刺激因子及核因子B激活因子配体诱导破骨细胞分化,实验组中分别加入含有或不含有硫酸钡的骨水泥颗粒。以抗酒石酸酸性磷酸酶阳性多核细胞及象牙磨片上虫蚀样骨吸收陷窝的形成昨作为检测破骨细胞形成及其骨吸收活性的检测指标,检验骨水泥中的硫酸钡对破骨细胞的影响。结果含或不含硫酸钡的骨水泥颗粒组抗酒石酸酸性磷酸酶阳性多核细胞形成均早于无骨水泥颗粒的对照组（4天vs6天）,而骨水泥颗粒中是否含有硫酸钡的两组间抗酒石酸酸性磷酸酶阳性多核细胞形成的时间无明显差异。各组间抗酒石酸酸性磷酸酶阳性多核细胞的数量无显著差异;含硫酸钡的骨水泥颗粒组象牙磨片上骨吸收陷窝的面积较不含硫酸钡的骨水泥颗粒组及阴性对照组均增大（28.26±4.98vs22.28±3.49vs14.58±2.82,〈0.05）。结论骨水泥颗粒中的硫酸钡能够促进破骨细胞分化并促进成熟破骨细胞的骨吸收活性。     

The effects of hyaluronan on bone resorption and bone mineral density in a rat model of estrogen deficiency-induced osteopenia

Hyaluronan, or hyaluronic acid (HA), is an essential component of extracellular matrices. HA of appropriate molecular weight and concentration can induce osteoblast differentiation and bone formation in vitro. The aim of our study was to evaluate the effects of HA of different molecular weights on ovariectomy (OVX)-induced bone loss in rats. Adult female Sprague Dawley rats were subjected to bilateral OVX or sham surgical procedure (sham). OVX rats were treated with: HA of molecular weight of 0.75 MDa at a dose of 1 mg/kg/day and with HA of molecular weight of 1.62 MDa at a dose of both 0.5 mg/kg/day and 1 mg/kg/day. HA was applied orally once a day during the 8-week period after ovariectomy. Body weight, urinary pyridinoline (Pyr), deoxypyridinoline (DPyr) corrected for urinary creatinine, serum nitrite/nitrate concentrations and whole body and femoral bone mineral density (BMD) were measured. HA treatment had no effect on the body weight gain in OVX rats. Excretion of urinary Pyr and Dpyr significantly increased in OVX rats compared to sham controls. The higher molecular weight HA (1.62 MDa) significantly reduced urinary Pyr and DPyr concentrations measured on day 28 after ovariectomy (p < 0.001). Serum concentrations of nitric oxide metabolites, nitrite/nitrate significantly decreased in OVX rats in comparison with sham controls (p < 0.001). HA of both 0.75 MDa and 1.62 MDa molecular weights significantly enhanced serum nitrite/nitrate concentrations in OVX rats. There was a clear reduction of whole body and femoral BMD in untreated OVX rats. The higher molecular weight HA decreased both whole body and femoral BMD loss. Our results show that orally applied HA of high molecular weight (1.62 MDa) inhibits bone resorption and provides a protective effect on bone density in ovariectomized rats.     

Effects of estrogen, raloxifene, and hormone replacement therapy on serum C-reactive protein and homocysteine levels

OBJECTIVES: To investigate the effects of conjugated equine estrogen (CEE), CEE plus medroxyprogesterone acetate (MPA), CEE plus Nomegestrol acetate (NA), and raloxifene on serum high sensitivity C-reactive protein (hs-CRP) and homocysteine (Hcy) levels in healthy postmenopausal women. MATERIALS: One hundred seven healthy postmenopausal women were recruited in a prospective, randomized, and placebo-controlled 6 months study. Of these, 18 were hysterectomized and received daily oral 0.625 mg CEE. Eighty nine non-hysterectomized women were randomly allocated to one of four groups: a group (22 patients) treated with CEE, 0.625 mg/daily plus MPA 2.5 mg/daily; a group (22 patients) treated with CEE, 0.625 mg/daily plus NA 5 mg/daily; a group (23 patients) treated with raloxifene hydrochloride, 60 mg once daily; and a placebo group (22 patients). Hcy and hs-CRP were measured at baseline and at 3 and 6 months. RESULTS: CEE (20%, P=0.03) and CEE+MPA (59%, P=0.006) increased serum hs-CRP levels significantly, whereas CEE+NA decreased serum hs-CRP by 25% (P=0.01). Raloxifene had no significant effect on serum hs-CRP levels during and after the treatment. In all active treatment groups serum Hcy levels decreased significantly compared to baseline and placebo. CONCLUSIONS: Conjugated equine estrogen, hormone replacement therapies, and raloxifene lower serum Hcy levels to a comparable extent in postmenopausal women. Hs-CRP, as a cardiovascular risk factor, is not influenced by raloxifene, whereas CEE and CEE plus MPA significantly increase hs-CRP levels. Treatment with CEE plus NA reduces serum hs-CRP levels.     

Effect of adrenal steroids on bone resorption in rats.

Rats labeled with strontium-85 (85Sr) were rejected with adrenocortical steroids for 2 wk. The urinary-to-tibial (U/T) 85Sr ratio was used as an index of bone resorption. The glucocorticoids caused an inhibition of skeletal resorption, as judged by the 50% reduction in the U/T ratio, and decreased excretion of hydroxyproline. Thyroidal calcitonin levels were slightly elevated in glucocorticoid-treated animals, suggestive of a possible retardation of calcitonin release. The U/T ratios of thyroparathyroidectomized (TPTX) rats injected with corticosteroids were 50% of control values. The results indicate that glucocorticoids inhibit bone resorption independent of the action of calcitonin. Cortisol treatment increased the tibial density as measured by a radiographic technique. However, bone density was decreased and the U/T ratio increased in steroid-treated rats fed a low-calcium diet. In TPTX cortisol-treated rats, parathyroid extract (PTE) increased the U/T ratio and serum calcium but not to the degree observed in TPTX PTE-injected control animals. These experiments indicate that in rats glucocorticoids inhibit the rate of bone resorption but this effect can be overcome in part by PTE.     

Effect of mineral content of human bone on in vitro resorption

Summary Osteoclasts, mechanically isolated from chick long bones, were grown in vitro on slices of human rib and femur. Evidence of their activity was assessed by secondary electron and backscattered electron (BSE) imaging in the SEM. BSE imaging was also used to study the relative degree of mineralisation of the bone matrix in which resorption had taken place. All bone phases were resorbed, from osteoid through to densely mineralised interstitial bone and reversal (cement) lines. Resorbing osteoclasts crossed reversal lines between osteons of different mineral density and moved both from higher to lower and lower to higher density phases. Where single loci spanned reversal lines, and thus breached bone of two different mineral densities, depth of demineralisation was inversely related to mineral density. The presence of an annular zone around some resorption loci, which may be caused by demineralisation beneath the osteoclast clear zone, was confirmed. Also, BSE imaging of polished substrata showed that significantly more osteoclastic activity had occurred at their surfaces than was apparent from the amount of cavitation present.     

Effect of Pasteurella multocida toxin on bone resorption in vitro.

Pasteurella multocida toxin (PMT), which is the primary etiologic factor in the pathogenesis of progressive atrophic rhinitis in pigs, was found to stimulate bone resorption in vitro. This stimulation was observed both in cultures of murine calvaria by measuring the release of calcium and of the lysosomal enzyme beta-glucuronidase and in murine long bone cultures by measuring the release of calcium. Both systems showed the same dose response curve, with the maximal effect at a concentration of 5 ng/ml. The effect on calvaria was studied in more detail. PMT increased bone resorption 24 h after its addition and always had to be present to express an effect. Calcitonin was able to inhibit this increase of resorption completely, and inhibitors of prostaglandin synthesis suppressed it partially. Although the data show an effect of PMT on bone tissue, the results do not exclude an action on cells in the nasal cavity, which could indirectly stimulate bone resorption.     

Effect of MALP-2, a lipopeptide from Mycoplasma fermentans, on bone resorption in vitro

Mycoplasmas may be associated with rheumatoid arthritis in various animal hosts. In humans, mycoplasma arthritis has been recorded in association with hypogammaglobulinemia. Mycoplasma fermentans is one mycoplasma species considered to be involved in causing arthritis. To clarify which mycoplasmal compounds contribute to the inflammatory, bone-destructive processes in arthritis, we used a well-defined lipopeptide, 2-kDa macrophage-activating lipopeptide (MALP-2) from M. fermentans, as an example of a class of macrophage-activating compounds ubiquitous in mycoplasmas, to study its effects on bone resorption. MALP-2 stimulated osteoclast-mediated bone resorption in murine calvaria cultures, with a maximal effect at around 2 nM. Anti-inflammatory drugs inhibited MALP-2-mediated bone resorption by about 30%. This finding suggests that MALP-2 stimulates bone resorption partially by stimulating the formation of prostaglandins. Since interleukin-6 (IL-6) stimulates bone resorption, we investigated IL-6 production in cultured calvaria. MALP-2 stimulated the liberation of IL-6, while no tumor necrosis factor was detectable. Additionally, MALP-2 stimulated low levels of NO in calvaria cultures, an effect which was strongly increased in the presence of gamma interferon, causing an inhibition of bone resorption. MALP-2 stimulated the bone-resorbing activity of osteoclasts isolated from long bones of newborn rats and cultured on dentine slices without affecting their number. In bone marrow cultures, MALP-2 inhibited the formation of osteoclasts. It appears that MALP-2 has two opposing effects: it increases the bone resorption in bone tissue by stimulation of mature osteoclasts but inhibits the formation of new ones.     

A prospective longitudinal study of urinary excretion of a bone resorption marker in adolescents

In growing subjects, the rates of bone resorption and bone deposition are substantially larger than in non-growing individuals. The purpose of this study was to measure the urinary excretion of a specific bone resorption marker in function of adolescent growth stages in a prospective longitudinal study. A cohort of 60 adolescents (28 male and 32 female) was followed for 3.4 years (range 1.7-4.6 years). Monthly measurements of height, weight and urinary excretion of a bone resorption marker, collagen type I N-telopeptides (NTx), were made. Changes in standing height were used to classify the adolescents into one or more of six adolescent growth stages: pre-pubertal growth (continuous moderate growth rate), ascending growth spurt (increasing growth rate), peak growth spurt (growth rate higher than 7cm/year for at least 6 months), descending growth spurt (continuous decrease in growth rate), end of growth (growth rate between 0 and 2cm/year), and no growth. An increase in NTx excretion from the pre-pubertal to peak growth spurt of about 33% was found (44% and 27% for females and males respectively). The decreasing growth rate after the pubertal growth spurt coincided with a clear decrease in NTx excretion. These differences were statistically significant, except between the prepubertal and ascending growth stage. Individual mean NTx excretion during each growth stage was correlated with the individual's growth rate during that time (r = 0.81). There was large inter-and intra individual variability. In non-growing adolescents (growth rate 0cm/y) NTx excretion levels were 4-7 times greater than in adults. In all females, menarche was followed by a decrease in NTx excretion. In conclusion, the excretion of a specific bone resorption marker, NTx, was correlated with the changes in growth rate during adolescence, both for males and females. There were large inter and intra-individual differences in NTx excretion during the different growth stages. In adolescents who reached their adult height at the end of the pubertal growth spurt, bone resorption decreased dramatically but remained 4-7 fold higher than in adults.     

A prospective longitudinal study of urinary excretion of a bone resorption marker in adolescents

In growing subjects, the rates of bone resorption and bone deposition are substantially larger than in non-growing individuals. The purpose of this study was to measure the urinary excretion of a specific bone resorption marker in function of adolescent growth stages in a prospective longitudinal study. A cohort of 60 adolescents (28 male and 32 female) was followed for 3.4 years (range 1.7-4.6 years). Monthly measurements of height, weight and urinary excretion of a bone resorption marker, collagen type I N-telopeptides (NTx), were made. Changes in standing height were used to classify the adolescents into one or more of six adolescent growth stages: pre-pubertal growth (continuous moderate growth rate), ascending growth spurt (increasing growth rate), peak growth spurt (growth rate higher than 7 cm/year for at least 6 months), descending growth spurt (continuous decrease in growth rate), end of growth (growth rate between 0 and 2 cm/year), and no growth. An increase in NTx excretion from the pre-pubertal to peak growth spurt of about 33% was found (44% and 27% for females and males respectively). The decreasing growth rate after the pubertal growth spurt coincided with a clear decrease in NTx excretion. These differences were statistically significant, except between the prepubertal and ascending growth stage. Individual mean NTx excretion during each growth stage was correlated with the individual's growth rate during that time (r = 0.81). There was large inter-and intra individual variability. In non-growing adolescents (growth rate 0 cm/y) NTx excretion levels were 4-7 times greater than in adults. In all females, menarche was followed by a decrease in NTx excretion. In conclusion, the excretion of a specific bone resorption marker, NTx, was correlated with the changes in growth rate during adolescence, both for males and females. There were large inter and intra-individual differences in NTx excretion during the different growth stages. In adolescents who reached their adult height at the end of the pubertal growth spurt. bone resorption decreased dramatically but remained 4-7 fold higher than in adults.     

Effect of estrogen use on tooth retention, oral bone height, and oral bone porosity in Japanese postmenopausal women

OBJECTIVE: Recent studies in the United States support the protective effect of estrogen use on tooth retention; however, little is known as to how estrogen promotes tooth retention. The aims of this study were to investigate the effects of estrogen use on tooth retention, oral bone height, and oral bone porosity in Japanese postmenopausal women and to clarify how estrogen promotes tooth retention. DESIGN: Relationships among the number of teeth remaining (total, anterior, and posterior teeth), oral bone height, oral bone porosity, bone mineral density of the lumbar spine and the femoral neck, estrogen use status, and the duration of estrogen use were evaluated in 330 Japanese postmenopausal women (mean age +/- SD, 56.8 +/- 7.6 y). RESULTS: Analysis of covariance adjusted for confounding variables revealed that estrogen users (66 women) tended to have more posterior teeth than did nonusers (264 women) (P = 0.065), although there were no significant differences in number of total (P = 0.196) and anterior (P = 0.751) teeth remaining, oral bone height (P = 0.970), oral bone porosity (P = 0.745), and bone mineral density of the lumbar spine (P = 0.459) and the femoral neck (P = 0.749) between estrogen users and nonusers. Multiple regression analysis showed that the duration of estrogen use was significantly associated with number of total (P = 0.019) and posterior (P = 0.007) teeth remaining, independent of age and oral bone height. CONCLUSION: Our results suggest that estrogen may promote tooth retention by strengthening the periodontal attachment surrounding the teeth, but not increasing oral bone height and not decreasing oral bone porosity.     

Forearm bone density and grip strength in women after menopause,with and without estrogen replacement therapy

Peaking in young adulthood, both bone mass and muscle strength decrease with ageing, but bone loss may accelerate after the menopause and can be delayed by estrogen replacement therapy (ERT). This study was designed to evaluate whether, like bone density, the muscle strength was affected by the onset of menopause and/or ERT. First grip strength (GS) of young female adults (group III; n = 18; age (± S.E.M.) 21.8 ± 0.4 years) was compared to that of postmenopausal women, who were divided into two groups. Group I (n = 22; age 59.6 ± 1.6 years) was 12.5 ± 1.7 years after the menopause and received no ERT, and group II (n = 21; age 59.5 ± 1.1 years) was 8.3 ± 1.2 years after the menopause and had received ERT for 3.9 ± 2.3 years at the time of the study. GS of the postmenopausal women was significantly (P < 0.005) lower than that of the young female adults. GS did not differ significantly between both postmenopausal groups. Further analysis revealed a weak negative correlation of years since menopause with forearm bone density (r = −0.37, P ≤ 0.023 for group II and III together), but not with GS. It is concluded that the later onset of menopause and estrogen replacement therapy do not seem to have a noticeable influence on muscle strength.