Glucocorticosteroid-induced osteoporosis in adult primiparous Göttingen miniature pigs: effects on bone mineral and mineral metabolism

Information on the pathophysiology of glucocorticoid-induced osteoporosis (GIO) is limited, since its clinical picture often reflects a combined effect of glucocorticoids (GC) and the treated systemic disease (i.e., inflammation and immobility). In 50 healthy adult (30-mo-old) primiparous G?ttingen minipigs, we studied the short-term (8 mo, n = 30) and long-term (15 mo, n = 10) effect of GC on bone and mineral metabolism longitudinally and cross-sectionally compared with a control group (n = 10). All animals on GC treatment received prednisolone orally at a dose of 1.0 mg x kg body wt(-1) x day(-1) for 8 wk and thereafter at 0.5 mg/kg body wt(-1) x day(-1). In the short term, GC reduced bone mineral density (BMD) at the lumbar spine by -47.5 +/- 5.1 mg/cm(3) from baseline (P < 0.001), which was greater (P < 0.05) than the loss [not significant (NS)] in the control group of -11.8 +/- 12.6 mg/cm(3). Calcium absorption decreased from baseline by -2,488 +/- 688 mg/7 days (P < 0.001) compared with -1,380 +/- 1,297 mg/7 days (NS) in the control group. Plasma bone alkaline phosphatase (BAP) decreased from baseline by -17.8 +/- 2.2 U/l (P < 0.000), which was significantly different (P < 0.05) from the value of the control group of -1.43 +/- 4.8 U/l. In the long term, the loss of BMD became more pronounced and bone mineral content (BMC), trabecular thickness, mechanical stability, calcium absorption, 25-hydroxyvitamin D(3), 1,25-dihydroxyvitamin D(3), and parathyroid hormone tended to be lower compared with the control group. There was a negative association between the cumulative dose of GC and BMD, which was associated with impaired osteoblastogenesis. In conclusion, the main outcomes after GC treatment are comparable to symptoms of GC-induced osteoporosis in human subjects. Thus the adult G?ttingen miniature pig appears to be a valuable animal model for GC-induced osteoporosis.     

Plasma monomeric calcitonin as a marker of disease activity in multiple myeloma patients with osteolysis.

Circulating monomeric human calcitonin (hCT-M), parathyroid hormone, osteocalcin, alkaline phosphatase, urinary hydroxyproline, corrected serum calcium and inorganic phosphate were measured in 49 multiple myeloma patients and 49 matched controls. In patients with Durie-Salmon stage III disease hCT-M levels (16.9 +/- 5.8 ng/l, mean +/- SD) were significantly higher than controls and stage I patients (P less than 0.01), and correlated directly with corrected serum calcium (r = 0.74; P less than 0.001). In the same subgroup 14 of 15 patients had plasma hCT-M concentrations higher than the mean + 2SD of the controls. The calcium infusion test induced an increase of hCT-M in normocalcemic patients which was significantly greater in patients with advanced disease than in either controls or stage I patients. These findings suggest that hCT-M may be a biochemical index of bone resorption and disease activity in myeloma patients with osteolysis. In fact, its plasma concentrations were elevated in a large proportion (93%) of patients with severe bone involvement, and correlated directly with serum calcium. Moreover, our findings suggest the presence of a calcitonin-dependent calcium homeostatic mechanism, that protects against hypercalcemia due to tumor osteolysis.     

Skeletal effects of oral oestrogen compared with subcutaneous oestrogen and testosterone in postmenopausal women.

STUDY OBJECTIVE--To compare oral and implanted oestrogens for their effects in preventing postmenopausal osteoporosis. DESIGN--Non-randomised cohort study of postmenopausal women treated with oral or depot oestrogens and postmenopausal controls. SETTING--Gynaecological endocrine clinic in tertiary referral centre. PATIENTS--Oral treatment group of 37 postmenopausal women (mean age 57.5 years, median 8.75 years from last menstrual period), compared with 41 women given oestrogen implants (mean age 56.2 years, median 9.5 years from last menstrual period) and 36 controls (mean age 51.8 years, median 2.0 years from last menstrual period). Weight was not significantly different among the groups. INTERVENTIONS--Oral treatment group was given continuous treatment with cyclic oestrogen and progesterone preparations (Prempak C or Cycloprogynova) for a median of 8.0 years. Implant group was given subcutaneous implants of oestradiol 50 mg combined with testosterone 100 mg, on average six monthly for a median of 8.5 years. Controls were not treated. END POINT--Significant increase in bone density. MEASUREMENTS AND MAIN RESULTS--Bone density measured by dual beam photon absorptiometry was 1.02 (SD 0.13) g hydroxyapatite/cm2 in implant group versus 0.89 (0.11) in oral group (p less than 0.01) and 0.87 (0.14) in controls (p less than 0.01). Serum oestradiol concentration in implant group was (median) 725 pmol/l versus 170 pmol/l in oral group (p less than 0.01) and 99 pmol/l in controls (p less than 0.01). Serum follicular stimulating hormone was median 1 IU/l (range 1-11) in implant group (equivalent to premenopausal values) versus 43 (4-94) IU/l in oral group (p less than 0.01) and 72 (28-99) IU/l in controls (p less than 0.01). CONCLUSIONS--Subcutaneous oestrogen is more effective than oral oestrogen in preventing osteoporosis, probably owing to the more physiological (premenopausal) serum oestradiol concentrations achieved. It also avoids problems of compliance that occur with oral treatment.     

Neuromuscular and hormonal adaptations in athletes to strength training in two years

Neuromuscular and hormonal adaptations to prolonged strength training were investigated in nine elite weight lifters. The average increases occurred over the 2-yr follow-up period in the maximal neural activation (integrated electromyogram, IEMG; 4.2%, P = NS), maximal isometric leg-extension force (4.9%, P = NS), averaged concentric power index (4.1%, P = NS), total weight-lifting result (2.8%, P less than 0.05), and total mean fiber area (5.9%, P = NS) of the vastus lateralis muscle, respectively. The training period resulted in increases in the concentrations of serum testosterone from 19.8 +/- 5.3 to 25.1 +/- 5.2 nmol/l (P less than 0.05), luteinizing hormone (LH) from 8.6 +/- 0.8 to 9.1 +/- 0.8 U/l (P less than 0.05), follicle-stimulating hormone (FSH) from 4.2 +/- 2.0 to 5.3 +/- 2.3 U/l (P less than 0.01), and testosterone-to-serum sex hormone-binding globulin (SHBG) ratio (P less than 0.05). The annual mean value of the second follow-up year for the serum testosterone-to-SHBG ratio correlated significantly (r = 0.84, P less than 0.01) with the individual changes during the 2nd yr in the averaged concentric power. The present results suggest that prolonged intensive strength training in elite athletes may influence the pituitary and possibly hypothalamic levels, leading to increased serum levels of testosterone. This may create more optimal conditions to utilize more intensive training leading to increased strength development.     

Total body calcium in rheumatoid arthritis: effects of disease activity and corticosteroid treatment.

Rheumatoid arthritis may be associated with generalised as well as periarticular osteoporosis. To assess the extent of bone loss and the influence of corticosteroid treatment total body calcium was measured by in-vivo neutron activation analysis in 63 patients with rheumatoid arthritis treated with non-steroidal anti-inflammatory drugs alone and 31 treated with additional low-dose corticosteroids. The results were compared with those in 40 normal controls matched for age, sex, and menopausal state. There were significant reductions in mean total body calcium in the group treated with non-steroidal anti-inflammatory drugs (5.3% in men; 6.8% in women) and greater reductions in the corticosteroid-treated patients (11.5% in men, 15.5% in women). The reduction was correlated with disease duration and activity in the patients treated with non-steroid anti-inflammatory drugs alone. Measured total body calcium was significantly less than the values predicted when this relation was used in the corticosteroid-treated patients. The data suggest that increased bone loss in patients with rheumatoid arthritis treated with corticosteroids is attributable to drug treatment rather than disease activity. Many patients with rheumatoid arthritis treated with low-dosage corticosteroids and some postmenopausal women with the disease are likely to be at risk from the complications of osteoporosis.     

Calcitonin induced increase in ACTH, beta-endorphin and cortisol secretion

The response of ACTH, beta-endorphin and cortisol to calcitonin administration was investigated in 8 subjects with recent fractures of the vertebrae due to postmenopausal or senile osteoporosis (Ost) and in seven normal healthy controls (NC). A significant increase of the three hormones was observed in 13 subjects. The maximum increase was observed between 15 and 60 min.: the cortisol level (microgram/100 ml) rose from 14.3 +/- 1.9 to 24.8 +/- 3.2 (P less than 0.05) in Ost and from 7.7 +/- 0.6 to 21.7 +/- 1.7 (P less than 0.001) in NC, the beta-endorphin (pmol/l) from 5.8 +/- 0.6 and to 21.2 +/- 1.3 in OST (P less than 0.001) and from 5.9 +/- 0.4 to 21.9 +/- 4.5 (P less than 0.01) in NC and the ACTH levels (pg/ml) from 21.3 +/- 5.7 to 61.7 +/- 3.6 (P less than 0.001) in OST and from 30.0 +/- 6.2 to 58.8 +/- 7.5 (P less than 0.05) in NC. The results indicate a possible role of calcitonin in modulating the anterior pituitary function. It also suggests that the analgesic effect of calcitonin might be mediated by the increase of beta-endorphin. The possibility that this analgesic effect of calcitonin is due to its direct binding to the opiate receptors was excluded in the present study by in vitro binding assay.     

Calcitonin, estrogens and the bone

Estrogen deficiency following natural or surgical menopause, is thought to be the main factor leading to postmenopausal bone loss. Furthermore, after estrogen failure a significant reduction of intestinal calcium absorption and a negativization of calcium balance has been observed. The mechanism of estrogen effect on skeletal tissue is not yet fully elucidated. Recently, specific receptors for estrogens in osteoblastic cells have been described; however their low density does not give a full explanation about their functional role. Therefore estrogens act, at least in part, indirectly through calciotropic hormones. In order to further elucidate this issue, we performed some studies in postmenopausal osteoporotic patients and in fertile oophorectomized women. In the first double blind placebo controlled study, after a 1-year estrogen treatment period we observed an increase in bone mineral content in the hormone-treated patients. Furthermore, in all treated patients an improvement of intestinal calcium absorption was detected, while 1,25-dihydroxy-vitamin D serum levels did not show significant changes. To further analyse the relationship between estrogens (E) and calcitonin (CT) in postmenopausal osteoporosis, we performed a double blind placebo controlled study to evaluate the effects of 1-yr estro-progestative treatment on CT secretory reserve, evaluated by calcium infusion test. Blood levels of CT showed a progressive increase during the study period in the hormone-treated group, with a significant increase in the CT response to calcium stimulation test, suggesting a modulation of CT secretion by E. Recently, we performed two studies in fertile oophorectomized women. In the first, we followed longitudinally 24 fertile women for 1 yr. In these patients we measured, before and after oophorectomy, biochemical indexes of bone metabolism and bone mass. During the observation period a significant increase in bone resorption and a significant drop in intestinal calcium absorption was observed. In the second study, performed on 14 women before and 6 months after oophorectomy, a treatment with conjugated estrogens allowed the correction of the primary intestinal defect responsible for the reduced calcium absorption.(ABSTRACT TRUNCATED AT 400 WORDS)     

Treatment of spinal osteoporosis in postmenopausal women.

Ninety-five postmenopausal women with unequivocably wedged or compressed vertebrae in whom the recognised causes of secondary osteoporosis had been excluded were studied, 41 having no treatment and the rest one or more of six different treatments. The treatment regimens comprised calcium supplements, vitamin D, calcium and vitamin D, ethinyloestradiol or--where oestrogens were contraindicated--norethisterone, 1 alpha-hydroxycholecalciferol (1 alpha-OHD3), or hormones with 1 alpha-OHD3. The seven groups were reasonably comparable in most respects except that the hormone-treated patients were younger and had a higher initial cortical area ratio than the others, and the calcium- and hormone-treated groups had the best initial radio-calcium absorption. The untreated osteoporotic patients lost cortical bone more rapidly than do normal postmenopausal women. Three treatments (calcium, hormones, and 1 alpha OHD3 plus hormones) appear to be useful in modifying the disease, and two treatments (vitamin D and 1 alpha-OHD3) useless or even harmful. Vitamin D and 1 alpha-OHD3 are more safely used in conjunction with oestrogens, which protect bone against resorption, than on their own.     

Role of peak bone mass and bone loss in postmenopausal osteoporosis: 12 year study.

OBJECTIVE--To examine the role of peak bone mass and subsequent postmenopausal bone loss in the development of osteoporosis and the reliability of identifying women at risk from one bone mass measurement and one biochemical assessment of the future bone loss. DESIGN--Population based study. SETTING--Outpatient clinic for research into osteoporosis. SUBJECTS--178 healthy early postmenopausal women who had participated in a two year study in 1977. 154 of the women underwent follow up examination in 1989, of whom 33 were excluded because of diseases or taking drugs known to affect calcium metabolism. MAIN OUTCOME MEASURES--Bone mineral content of the forearm and values of biochemical markers of bone turnover. RESULTS--The average reduction in bone mineral content during 1977-89 was 20%, but the fast losers had lost 10.0% more than had the slow loser group (mean loss 26.6% in fast losers and 16.6% in slow losers; p less than 0.001). Prediction of future bone mineral content using baseline bone mineral content and estimated rate of loss gave results almost identical with the actual bone mineral content measured in 1989. Seven women had had a Colles'' fracture and 20 a spinal compression fracture. The group with Colles'' fracture had low baseline bone mineral content (34.7 (95% confidence interval 31.3 to 38.1) units v 39.4 (38.1 to 40.8) units in women with no fracture) whereas the group with spinal fracture had a normal baseline bone mineral content (38.1 (35.0 to 41.1) units) but an increased rate of loss (-2.4 (-3.5 to -1.3)%/year v -1.8 (-2.1 to -1.5)%/year in women with no fracture). CONCLUSIONS--One baseline measurement of bone mass combined with a single estimation of the rate of bone loss can reliably identify the women at menopause who are at highest risk of developing osteoporosis later in life. The rate of loss may have an independent role in likelihood of vertebral fracture.     

Hormone replacement therapy,calcium and vitamin D<Subscript>3</Subscript> versus calcium and vitamin D<Subscript>3</Subscript>alone decreases markers of cartilage and bone metabolism in rheumatoid arthritis: a randomized controlled trial [ISRCTN46523456]

This study aimed to evaluate the effects of hormone replacement therapy (HRT), known to prevent osteoporosis and fractures, on markers of bone and cartilage metabolism. Furthermore, we assessed whether changes in these markers corresponded to alterations in bone mineral density and radiographic joint destructions in postmenopausal women with rheumatoid arthritis. Eighty-eight women were randomized to receive HRT, calcium, and vitamin D3, or calcium and vitamin D3 alone, for 2 years. Bone turnover was studied by analyzing serum levels of C-terminal telopeptide fragments of type I collagen (CTX-I), C-terminal telopeptide of type I collagen (ICTP), bone sialoprotein, and C-terminal propeptide of type I procollagen (PICP) and cartilage turnover by urinary levels of collagen type II C-telopeptide degradation fragments (CTX-II) and cartilage oligomeric matrix protein (COMP) in serum. Treatment with HRT resulted in decrease in CTX-I (P < 0.001), ICTP (P < 0.001), PICP (P < 0.05), COMP (P < 0.01), and CTX-II (P < 0.05) at 2 years. Reductions in CTX-I, ICTP, and PICP were associated with improved bone mineral density. Of the markers tested, CTX-I reflected bone turnover most sensitively; it was reduced by 53 +/- 6% in the patients receiving HRT. Baseline ICTP (P < 0.001), CTX-II (P < 0.01), and COMP (P < 0.05) correlated with the Larsen score. We suggest that biochemical markers of bone and cartilage turnover may provide a useful tool for assessing novel treatment modalities in arthritis, concerning both joint protection and prevention of osteoporosis.     

Effect of elastic loading on ventilatory pattern during progressive exercise

Ventilatory responses to progressive exercise, with and without an inspiratory elastic load (14.0 cmH2O/l), were measured in eight healthy subjects. Mean values for unloaded ventilatory responses were 24.41 +/- 1.35 (SE) l/l CO2 and 22.17 +/- 1.07 l/l O2 and for loaded responses were 24.15 +/- 1.93 l/l CO2 and 20.41 +/- 1.66 l/l O2 (P greater than 0.10, loaded vs. unloaded). At levels of exercise up to 80% of maximum O2 consumption (VO2max), minute ventilation (VE) during inspiratory elastic loading was associated with smaller tidal volume (mean change = 0.74 +/- 0.06 ml; P less than 0.05) and higher breathing frequency (mean increase = 10.2 +/- 0.98 breaths/min; P less than 0.05). At levels of exercise greater than 80% of VO2max and at exhaustion, VE was decreased significantly by the elastic load (P less than 0.05). Increases in respiratory rate at these levels of exercise were inadequate to maintain VE at control levels. The reduction in VE at exhaustion was accompanied by significant decreases in O2 consumption and CO2 production. The changes in ventilatory pattern during extrinsic elastic loading support the notion that, in patients with fibrotic lung disease, mechanical factors may play a role in determining ventilatory pattern.     

Effects of dietary NaCl supplementation on bone synthesis of hydroxyproline, urinary hydroxyproline excretion and bone 45Ca uptake in the rat

High sodium chloride intakes are regarded as a risk factor for osteoporosis because they increase the obligatory urinary calcium loss and stimulate parathyroid activity. Sodium chloride loads induce osteopenia in the rat. The effect could be due to a decrease in bone formation or a rise in bone resorption. Two experiments were undertaken to study the effects of dietary NaCl supplementation on 3H-hydroxyproline synthesis and 45Ca uptake in femoral bone. Salt-treated rats excreted 1.7 times more total urinary hydroxyproline (P less than 0.001) and 2.1 times more recently labelled 3H-hydroxyproline than controls (P less than 0.02) but they did not accumulate less 3H-hydroxyproline or less 45Ca in their bones than controls. These results indicate that salt-mediated osteopenia is due to an increase in bone resorption, rather than to a decrease in bone formation.     

Relationship between serum albumin and bone mineral density in postmenopausal women and in patients with hypoalbuminemia.

Some discrepancies exist about the relationship between serum albumin level and the pathogenesis of osteoporosis; moreover, most of the studies available have especially concerned patients with osteoporosis, often associated with fractures. Our study, therefore, aims to investigate the presence of a relationship between serum albumin level and bone mineral density in a group of healthy women (n=650; mean age 59.0 +/- 7.4 years) who voluntarily underwent screening for osteoporosis only because they were menopausal (11.2 +/- 7.4 years since menopause) and, for comparison, in a group of outpatients (n = 44; mean age 57.6 +/- 7.0 years; 9.1 +/- 6.7 years since menopause) with hypoalbuminemia associated with diseases. The results show a lack of any relationship in healthy women between serum albumin value and bone mineral density; the lack of correlation was also shown when the postmenopausal women were down into normal, osteopenic and osteoporotic (WHO criteria) or in hypo, normal and hyperalbuminemic. The only significant parameters associated with lower bone mineral density, in fact, were age and years since menopause (p<0.0001 and p<0.0001 respectively at lumbar spine and p<0.02 and p<0.001 at femoral neck level). In the group of patients with hypoalbuminemia associated with diseases, on the other hand, a relationship between reduced bone mineral density and hypoalbuminemia was found (p<0.01 and p<0.05 respectively at lumbar spine and femoral neck). In conclusion, in healthy postmenopausal women the serum albumin level does not play a significant role in the pathogenesis of bone density reduction, which is mainly due to the number of years since menopause and advancing age. The hypoalbuminemia may be related to the reduction of bone mass only in the subjects affected by diseases associated with a significant albumin reduction.     

The effect of calcitonin treatment on plasma nitric oxide levels in post-menopausal osteoporotic patients

Several recent studies have revealed a wide role for nitric oxide (NO) in bone metabolism. Low doses of NO cause bone resorption, but higher doses of NO inhibit bone resorbing activity. Cytokines are potent stimulators of NO production. NO is a very short-lived molecules. It exists for only 6-10 s only before it is converted by oxygen and water into the end-products nitrates and nitrites. Osteoporosis is a metabolic bone disease, characterized by a decreased amount of bone and increased susceptibility to fracture. NO may be involved as a mediator of bone disease such as post-menopausal osteoporosis. Calcitonin is a peptide hormone that inhibits bone resorption. The function of calcitonin in some cells is often unclear. In this study 30 post-menopausal osteoporotic women of ages ranging between 55 and 59 years without systemic diseases and free of any drug therapy were included. Twenty of them, randomly chosen, were treated with calcium (500 mg day(-1))+calcitonin (nasal spray 100 U day(-1)) and the other 10 women (control group) were treated with calcium only. This treatment was applied for 6 months and NO values were measured in each of the two groups before and after treatment. Our findings demonstrate that NO regulates osteoclastic bone resorption activity in association with calcitonin.     

The effects of chronic vitamin A excess on bone remodeling in aged rats

This study was conducted to assess the effects of long-term ingestion of moderate excesses of vitamin A on trabecular bone remodeling in the fifth lumbar vertebral body of aged rats. Eighteen-month-old rats were fed diets with vitamin A content equal to the daily requirement (DR), 2-fold, and 5-fold the DR along with calcium content of either the DR or 0.3-fold the DR, for 14 months each. As expected, serum concentrations of 1,25-dihydroxyvitamin D were higher in the reduced than in the normal calcium intake groups (65.1 +/- 2.4 SEM vs 47.8 +/- 2.1 pg/ml, P less than 0.001). Calcium balance was more positive at the higher than the lower calcium intake (5.7 vs 0.9 mg, P less than 0.001) but was unaffected by vitamin A intake. Histomorphometric analysis of the fifth lumbar vertebral body revealed that the 2-fold but not the 5-fold excess in vitamin A intake resulted in a 15% increase in percentage of trabecular bone (P less than 0.02). The low calcium diet depressed bone growth (total bone tissue) but did not affect percentage of trabecular bone. Several effects of the vitamin A excess and low calcium diet were noted along the trabecular surface including increased mineral apposition rate and resorption surfaces and decreased formation surfaces. The net effect of vitamin A on trabecular bone of the rat varies as intake begins to exceed the DR. At a 2-fold excess, a modest favorable effect on percentage of trabecular bone was observed.     

miR-214对骨形成的抑制作用

越来越多的研究表明microRNA广泛参与骨代谢的调控,调节骨髓间充质干细胞、成骨及破骨细胞的增殖及分化,调控骨形成与骨吸收之间的平衡,在维持骨代谢平衡中发挥重要作用。近年来有研究报道老年性骨质疏松、绝经后骨质疏松均与miR-214的高表达有关。miR-214通过靶向作用于Osterix、ATF-4、FGFR1、Pten以及LZTS1等基因调控骨髓间充质干细胞、成骨细胞以及破骨细胞等骨组织细胞的增殖及分化,进而抑制骨形成,促进骨吸收。本文主要综述了miR-214对骨髓间充质干细胞、成骨细胞以及破骨细胞分化的调控作用,旨在探讨miR-214对骨形成的抑制作用,为骨质疏松等骨疾病的诊断及治疗提供理论依据。     

OPG/RANKL: role and therapeutic target in osteoporosis

Given the increasing risk of fractures with aging in western countries, there is a need for the development of safe and efficient anti-osteoporotic drugs for the prevention and treatment of osteoporosis. Recent studies have provided evidence for an essential role of RANKL (Receptor Activator of Nuclear Factor-kappa B Ligand) and its decoy receptor osteoprotegerin in the control of osteoclast differentiation and survival. Post-menopausal osteoporosis results from an imbalance between resorption and formation associated with decreased OPG/RANKL. Targeting the OPG/RANKL system may therefore have a beneficial impact in osteoporosis. Accordingly, the development of novel strategies targeting OPG/RANKL using anti-RANKL or therapeutic intervention proved to be efficient to reduce bone resorption and to prevent bone loss in postmenopausal osteoporosis. This opens the way for novel therapeutic strategies for correcting bone metabolism in various pathologic disorders characterized by increased bone remodelling and bone loss.     

Impact of the mass-reductive therapy with orlistat on 25-(OH)-D3 and PTH concentration in sera of obese, menopausal women

Epidemiological studies suggest a protective influence of obesity against postmenopausal bone loss. Lower risk of osteoporotic fractures was described in obese patients. However there were only a few studies which examined the effect of weight reduction on bone metabolism and results of these studies are controversial. The aim of the study was to evaluate the influence of weight reduction program using Orlistat on bone metabolism in perimenopausal women. Twenty obese women with simple obesity and without concomitant diseases (BMI 37.1 +/- 3.0 kg/m2, mean age 49.8 +/- 4.6 yrs) were enrolled into this study. The control group consisted of 20 healthy women (mean age 53.5 +/- 5.4 yrs, BMI 24.1 +/- 2.2 kg/m2). All patients have participated in a 3-month weight reduction therapy that consisted of: a 1000-1200 kcal/ day balanced diet (daily calcium consumption about 500mg), Orlistat 3 x 120mg a day and regular physical exercises. Before the weight reduction therapy and after 10% reduction of body weight, serum concentrations of PTH, 25-(OH)-D3, total calcium and phosphorus, total cholesterol were assessed. Dual energy x-ray absorptiometry (DEXA method) of lumbar spine and femoral neck, measuring BMD was performed once, after a 3-month weight reduction therapy using Lunar DPXL. All these measurements were performed only once in control subjects. After a 3-month weight reduction program in patients treated with Orlistat the mean weight loss was 11.6 +/- 5.1 kg which is 12.1 +/- 4.78 %. BMI decreased from 37.1 +/- 3.0 kg/m2 at baseline to 32.6 +/- 2.7 kg/m2 post-treatment. The body weight reduction resulted in significant decrease of body fat and total cholesterol concentration. In obese subjects serum concentration of 25-(OH)-D3 was significantly lower and serum concentration of PTH was significantly higher in comparison to healthy controls, both before and after weight reduction therapy. Serum concentration of PTH, 25-(OH)-D3, total calcium and phosphorus did not change significantly after therapy with Orlistat. Conclusion: 3-month weight reduction program using Orlistat did not influence significantly bone metabolism.     

Reduction of lecithin-cholesterol acyltransferase, apolipoprotein D and the Lp(a) lipoprotein with the anabolic steroid stanozolol

The effects of the anabolic steroid stanozolol (17-methyl-2H-5 alpha-androst-2-eno-(3,2-c)pyrazol-17 beta-ol) on lecithin-cholesterol acyltransferase, apolipoproteins B and D and the Lp(a) lipoprotein were determined in a prospective study of ten normolipidemic women with postmenopausal osteoporosis. Lecithin-cholesterol acyltransferase was reduced approx. 30% by 6 weeks of treatment with stanozolol (off treatment 5.1 +/- 1.2, on treatment 3.4 +/- 0.8 muml; P less than 0.02). The Lp(a) lipoprotein was reduced 65 +/- 23% by the steroid treatment (off treatment 5.5 +/- 5.5, on treatment 1.4 +/- 0.7 mg/dl; P less than 0.02). Apolipoprotein D was reduced 23 +/- 9% by the treatment (off treatment 5.9 +/- 0.9, on treatment 4.5 +/- 0.7 mg/dl; P less than 0.02). In contrast, apolipoprotein B increased slightly but insignificantly on steroid therapy (off treatment 90 +/- 21, on treatment 112 +/- 24 mg/dl). By 5 weeks after the drug was discontinued, all four of these proteins were near pretreatment levels. These significant changes in lipoprotein metabolism, combined with our previous report of reductions of HDL and particularly HDL2, suggest the need for caution in the long-term use of anabolic steroids.     

Variation of surface density and other parameters in remodeling of trabecular bone in various conditions

To appreciate the remodeling of the trabecular bone, the static morphometric parameters of surface density (SV(TRAB/BONE] and volumetric fraction (VV(TRAB/BONE] of cancellous bone were measured and compared to remodeling parameters, i.e., the surface extents of active/inactive resorption, active bone formation and nonmineralized bone. Iliac bone biopsies from 28 subjects with spasmophilia, osteoporosis and primary hyperparathyroidism were studied by means of a Nachet-France NS 2000 automatic image analyzer and a Zeiss ocular integrator; the results obtained in each group showed comparable values for the two methods (r = .8 for each group, with P less than .01). The remodeling parameters measured by means of the ocular integrator were compared with the variation measurements of the trabecular surface density, SV(TRAB/BONE). The correlation between the inactive osteoid surface and the coefficient of variation of the mean (CVM of SV(TRAB/BONE] on sections was significant for the three pathologic groups. The average mean values and standard errors of the mean of this latter parameter for the spasmophilia and hyperparathyroidic groups were, respectively, 0.063 +/- 0.008 and 0.092 +/- 0.012. Analysis of the experimental data shows that the simple global measurement of CVM (SV(TRAB/BONE] by means of an automatic image analyzer supplies information on the skeletal state during tissue remodeling.