Linking chronic tryptophan deficiency with impaired bone metabolism and reduced bone accrual in growing rats

There is increasing evidence that serotonin may regulate bone metabolism. However, its role remains to be clarified. Serotonin seems to be either beneficial or detrimental for bone tissues depending on the pharmacological manipulation used. In this study we evaluated the impact of a reduction of serotonergic stores induced by chronic tryptophan (TRP) depletion on various bone parameters in growing rats. For this purpose rats received a TRP‐free diet for 60 days. Bone mass, mineral content and density were measured by DXA and by pQCT in the appendicular skeleton. Bone metabolic markers included urinary deoxypyridinoline and serum osteocalcin measurements. IGF‐I levels were also evaluated. In TRP‐free diet rats, we found a decrease in body weight, a delayed femoral bone growth and bone mineral content as measured by DXA. pQCT analysis showed that these effects were related to a reduction of both cortical and trabecular bone and are associated with a reduction of bone strength. These effects are due to a negative shift in the balance between bone formation and resorption with a significant decrease in bone formation as evidenced by a reduction both in osteocalcin and IGF‐I levels. The present data extend our overall knowledge on the participation of serotonin in the regulation of growing bone and could be of interest in studying the impairment of bone growth in depressed subjects under particular condition of rapid bone accrual such as childhood and adolescence. J. Cell. Biochem. 107: 890–898, 2009. © 2009 Wiley‐Liss, Inc.     

Noninvasive markers of bone metabolism in the rhesus monkey: Normal effects of age and gender

Abstract: Measurement of bone turnover in conditions such as osteoporosis has been limited by the need for invasive iliac bone biopsy to reliably determine parameters of bone metabolism. Recent advances in the area of serum and urinary markers of bone metabolism have raised the possibility for noninvasive measurements; however, little nonhuman primate data exist for these parameters. The purpose of this experiment was to define the normal range and variability of several of the newer noninvasive bone markers which are currently under investigation in humans. The primary intent was to determine age and gender variability, as well as provide some normative data for future experiments in nonhuman primates. Twenty-four rhesus macaques were divided into equal groups of male and female according to the following age groupings: 3 years, 5–10 years, 15–20 years, and > 25 years. Urine was collected three times daily for a four-day period and measured for several markers of bone turnoverm including pyridinoline (PYD), deoxypyrodinoline (DPD), hydroxyproline, and creatinine. Bone mineral density measurements of the lumbar spine were performed at the beginning and end of the study period. Serum was also obtained at the time of bone densitometry for measurement of osteocalcin levels by radioimmunoassay. There were no significant differences in bone mineral density, urine PYD, or urine DPD based on gender. Bone density was lowest in the youngest animals, peaked in the 15–20-year group, but again decreased in the oldest animals. The osteocalcin, PYD, and DPD levels followed an inversely related pattern to bone density. The most important result was the relative age insensitivity of the ratio of PYD:DPD in monkeys up to age 20 years. Since bone density changes take months or years to become measurable and iliac biopsies are invasive, the PYD/DPD marker ratio may have important implications for rapid noninvasive measurement of the effects of potential treatments for osteoporosis in the non-human primate model.     

Height, bone mineral density and bone markers in congenital adrenal hyperplasia.

AIM: To evaluate height, bone growth, areal bone mineral density (aBMD), volumetric bone mineral density (vBMD) and markers of bone turnover in a group of patients affected by congenital adrenal hyperplasia (CAH). PATIENTS: There were 50 patients (23 males, 27 females), aged 1-28 years, affected by CAH due to 21-hydroxylase deficiency: 27 with the salt-wasting (SW); 14 with the simple virilizing (SV), and 9 with the nonclassical (NC) forms. METHODS: Bone morphometry was evaluated with the metacarpal index (MI) and lumbar aBMD and vBMD (L2-L4) by dual energy X-ray absorptiometry. Serum osteocalcin was used as a marker of bone formation, while urinary cross-linked N-telopeptides of type-I collagen and free deoxypyridinoline levels were evaluated as indexes of bone resorption. RESULTS: The height standard deviation score (SDS) was -0.41 +/- 1.4 in SW patients, -0.01 +/- 1.9 in SV patients, and -0.01 +/- 2.3 in NC patients. There was no significant difference among groups and against zero. The MI SDS was also not different between groups and against zero. aBMD was significantly lower in the pubertal patients compared with normal values, but only when patients with the SW and SV forms were considered together (p < 0.05). vBMD was significantly reduced in all patients with the classical form. Bone markers were not different in patients and controls. CONCLUSION: Our study shows that normal height can be attained in CAH patients; however, an impairment in bone growth and mineralization may be found in adolescents and young adults affected by the classical form.     

Immobilization on the day 14th does not disrupts the basic diurnal rhythm of bone resorption

Weight bearing and physical activity are important mechanical stimuli to bone growth and metabolism, and microgravity, such a space flight and/or bed rest, induces bone resorption and bone loss. An increased excretion of urinary Ca, an increased bone resorption and a decreased bone mineral density (BMD) have been observed in bed rest experiment of healthy subjects. Bone resorption markers show the specific circadian rhythms in human. Cross-linked carboxyl-terminal telopeptide of type I collagen (ICTP) and the urinary excretion of deoxypyridinoline (Dpy) are the highest in the early morning and the lowest late at night. Bed rest immobilization might influence these rhythms, due to no mechanical loading with loss of daily life activity. Bone resorption markers in healthy subjects had been compared between before and during bed rest to determine disruption of diurnal rhythms of bone resorption.     

HLA-B27 rats develop osteopaenia through increased bone resorption without any change in bone formation

Osteopaenia is a common complication of inflammatory bowel diseases (IBD). However, the mechanisms of bone loss are still the subject of debate. The aims of this study were to investigate bone loss in HLA-B27 transgenic rats, a spontaneous model of colitis and to compare the results provided by the usual markers of bone remodelling and by direct measurement of bone protein synthesis. Systemic inflammation was evaluated in HLA-B27 rats and control rats from 18 to 27 months of age. Then bone mineral density, femoral failure load, biochemical markers of bone remodelling and protein synthesis in tibial epiphysis were measured. Bone mineral density was lower in HLA-B27 rats than in controls. Plasma osteocalcin, a marker of bone formation, and fractional protein synthesis rate in tibial epiphysis did not differ between the two groups of rats. In contrast, urinary excretion of deoxypyridinoline, a marker of bone resorption, was significantly increased in HLA-B27 rats. The present results indicate that bone fragility occurs in HLA-B27 rats and mainly results from an increase in bone resorption. Systemic inflammation may be the major cause of the disruption in bone remodelling homeostasis observed in this experimental model of human IBD.     

VDR gene polymorphisms are overrepresented in german patients with type 1 diabetes compared to healthy controls without effect on biochemical parameters of bone metabolism.

Type 1 diabetic individuals are known to develop disorders of bone metabolism resulting in osteopenia. Previous studies have suggested an influence of vitamin D receptor alleles on bone metabolism and susceptibility for type 1 diabetes mellitus. The present study was initiated to investigate the distribution of vitamin D receptor alleles in Caucasian type 1 diabetic patients and their relation to bone turnover parameters. 75 patients were included and compared to 57 healthy controls. Three vitamin D receptor alleles were examined (BsmI, TaqI and FokI); serum levels of intact osteocalcin, parathyroid hormone, bone specific alkaline phosphatase, the carboxy terminal extension peptide of type I procollagen, 25-OH-vitamin D levels, HbA1c and urinary deoxypyridinoline excretion were measured. We observed a higher frequency of the TT genotype in diabetic patients, but no difference in markers of bone turnover between diabetics and non-diabetics in either sex. Bone turnover was different in men and in women without any association with vitamin D receptor genotype. No association was found between diabetes duration, age of onset or metabolic control and bone turnover parameters. In summary, our results show an association between the TT genotype and diabetes in Germans, but no difference in bone turnover markers between diabetics and non-diabetics.     

The effect of pramlintide (amylin analogue) treatment on bone metabolism and bone density in patients with type 1 diabetes mellitus.

Amylin is a 37-amino-acid peptide related to CGRP and calcitonin. It is co-secreted with insulin from pancreatic beta-cells. Amylin is deficient with type 1 diabetes mellitus. To study the in vivo effects of amylin in humans, diabetic patients are an adequate model of chronic amylin deficiency. We investigated the effect of a 12 months pramlintide therapy (amylin analogue) on bone metabolism in patients with type 1 diabetes mellitus. 23 patients with type 1 diabetes mellitus (age 45.2 +/- 10.3 years, duration of diabetes mellitus 20.7 +/- 9.8 years, 13 male, 10 female) injected themselves 0.1 ml pramlintide, a human amylin analogue, four times per day for a period of 12 months. Bone mineral density measurements of the lumbar spine by dual-energy X-ray absorptiometry (DXA), and biochemical markers of bone metabolism (serum-calcium, PTH, osteocalcin, urinary pyridinium cross-links) were obtained before and one year after starting pramlintide therapy. None of the following parameters changed significantly: bone density, serum calcium, PTH, osteocalcin or pyridinium cross-links. Only osteocalcin decreased from 7.205 ng/ml to 5.825 ng/ml, but this change was not statistically significant. We conclude that a one-year pramlintide therapy does not affect bone density or bone metabolism in patients with type 1 diabetes mellitus without osteopenia (based on the markers used).     

The effect of long-term glucocorticoids on bone metabolism in systemic lupus erythematosus patients: the prevalence of its anti-inflammatory action upon bone resorption

The study was made to evaluate bone turnover in systemic lupus erythematosus (SLE) patients undergoing long-term glucocorticoid therapy. Thirty-eight female patients with established SLE were compared with a control group consisting from 160 age-matched healthy women. Serum concentrations of proinflammatory cytokines: interleukin-1alpha, interleukin-6, tumor necrosis factor-alpha, granulocyte-macrophage colony stimulating factor (GM-CSF) and some biochemical markers of osteoporosis (osteocalcin, total and bone alkaline phosphatase, procollagen type I carboxyterminal propeptide, carboxyterminal telopeptides of type I collagen--CTx) were measured. Additionally, morning urine excretions of deoxypyridinoline and calcium/creatinin ratios were determined. The forearm densitometry (DXA) was performed in all patients. Bone mineral content (BMC) and bone mineral density (BMD) in the SLE group was not significantly different from the controls, and no relationship was found between the glucocorticoid exposure and the BMC/BMD. However, biochemical markers of bone resorption--CTx and calcium/creatinin ratio--were significantly increased in the patient group. Our results suggest that BMD/BMC is preserved in glucocorticoid-treated SLE patients despite accelerated bone turnover.     

Influence of clenbuterol on bone metabolism in exercised or sedentary rats.

This paper reports that the selective beta(2)-adrenergic receptor agonist clenbuterol affects bone metabolism in growing 3-mo-old male Wistar rats treated over 8 wk. Thirty-two 3-mo-old growing Wistar rats weighing 234 +/- 2 g were assigned to a progressive isometric force, strength-training exercise program plus oral clenbuterol (2 mg x kg body wt(-1) x day(-1)) for 5 days each week, exercise program without clenbuterol 5 days each week, no exercise program plus oral clenbuterol (2 mg x kg(-1) x day(-1)) for 5 days each week, or no exercise without clenbuterol 5 days each week. At the end of 8 wk, lean mass, fat mass, and right total femoral, distal metaphyseal femoral, and diaphyseal femoral bone mineral density were measured by Hologic QDR 4,500 dual X-ray absorptiometry (DEXA) technique. Left femoral bones were harvested after death on day 58, and femoral resistance was determined by three-point bending testing. We found that fat mass was decreased in rats given strength training exercise and decreased further in rats treated with clenbuterol. Lean mass was increased in clenbuterol-treated animals. Strength-training exercise appeared to have no effect on bone mineral density, serum osteocalcin, or urinary deoxypyridinoline. However, clenbuterol treatment decreased femoral length, diameter, bone mineral density, and mechanical resistance. Clenbuterol had no effect on osteocalcin but increased urinary deoxypyridinoline. We concluded that clenbuterol treatment decreased bone mineral density and increased bone resorption independent of the level of exercise rats were given.     

Action of green tea catechin on bone metabolic disorder in chronic cadmium-poisoned rats

The purpose of this study was to investigate the effects of green tea catechin on bone metabolic disorders and its mechanism in chronic cadmium-poisoned rats. Sprague-Dawley male rats weighing 100+/-10 g were randomly assigned to one control group and three cadmium-poisoned groups. The cadmium groups included a catechin free diet (Cd-0C) group, a 0.25% catechin diet (Cd-0.25C) group and a 0.5% catechin diet (Cd-0.5C) group according to their respective levels of catechin supplement. After 20 weeks, the deoxypyridinoline and crosslink values measured in urine were significantly increased in the Cd-0C group. Cadmium intoxication seemed to lead to an increase in bone resorption. In the catechin supplemented group (Cd-0.5C group), these urinary bone resorption marks, were decreased. The serum osteocalcin content in the cadmium-poisoned group was significantly increased as compared with the control group. In the catechin supplemented group serum osteocalcin content values were lower than the control group. The cadmium-intoxicated group (Cd-0C group), had lower bone mineral density than the control group (total body, vertebra, pelvis, tibia and femur). The catechin supplement increased bone mineral density to about the same as the control group. Bone mineral content showed a similar trend to total bone mineral density. Therefore, the bone mineral content of the Cd-0C group at the 20th week was significantly lower than the control group. The catechin supplemented group (Cd-0.5C group) was about the same as the control group. The cause of decreasing bone mineral density and bone mineral content by cadmium poisoning was due to the fast bone turnover rate, where bone resorption occurred at a higher rate than bone formation. The green tea catechin aided in normalizing bone metabolic disorders in bone mineral density, bone mineral content and bone calcium content caused by chronic cadmium intoxication.     

Effects of 0.4 T rotating magnetic field exposure on density, strength, calcium and metabolism of rat thigh bones

The current study investigated the effects of 0.4 T rotary non-uniform magnetic field (RMF) exposure on bone density in ovariectomized (OVX) rats. Results showed that many bone indexes are significantly elevated after RMF exposure compared to the control OVX group and confirmed mechanistic evidence that strong magnetic field (MF) exposure could effectively increase bone density and might be used to treat osteoporosis. Synergy of daily RMF exposure (30 min a day for 30 days using an 8 Hz rotary 0.4 T MF) with calcium supplement tended to increase the indexes of thigh bone density, energy absorption, maximum load, maximum flexibility, and elastic deformation as compared to those of untreated OVX control group. Results also revealed that the indexes of alkaline phosphatase (ALP), serum phosphate, and serum calcium were higher in rats exposed to RMF with calcium than in the untreated OVX control group. Changes in bone mineral density (BMD) and bone mineral content (BMC) were observed in rats for three months including the first month RMF exposure. Bone density in rats exposed each day for 60 min increased during 1-month exposure and continued to increase during the post-exposure period. Furthermore, bone density and calcium content in rats exposed for 90 min daily decreased initially in the exposure month; however, ratio of increase was well above the control values by the end of the post-exposure period suggesting possible window and delayed effects. The study indicated that RMF exposure to both male and OVX female rats for 120 min a day over 15 day period should effectively promote increase of bone calcium contents (BCC) and bone-specific alkaline phosphatase (BAP) in rats thigh bone as well as a corresponding decrease in deoxypyridinoline crosslinks (DPD).     

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.     

Milk intake and bone mineral acquisition in adolescent girls: randomised,controlled intervention trial.

OBJECTIVES: To investigate the effect of milk supplementation on total body bone mineral acquisition in adolescent girls. DESIGN: 18 month, open randomised intervention trial. SUBJECTS: 82 white girls aged 12.2 (SD 0.3) years, recruited from four secondary schools in Sheffield. INTERVENTION: 568 ml (one pint) of whole or reduced fat milk per day for 18 months. MAIN OUTCOME MEASURES: Total body bone mineral content and bone mineral density measured by dual energy x ray absorptiometry. Outcome measures to evaluate mechanism included biochemical markers of bone turnover (osteocalcin, bone alkaline phosphatase, deoxypyridinoline, N-telopeptide of type I collagen), and hormones important to skeletal growth (parathyroid hormone, oestradiol, insulin-like growth factor I). RESULTS: 80 subjects completed the trial. Daily milk intake at baseline averaged 150 ml in both groups. The intervention group consumed, on average, an additional 300 ml a day throughout the trial. Compared with the control group, the intervention group had greater increases of bone mineral density (9.6% v 8.5%, P = 0.017; repeated measures analysis of variance) and bone mineral content (27.0% v 24.1%, P = 0.009). No significant differences in increments in height, weight, lean body mass, and fat mass were observed between the groups. Bone turnover was not affected by milk supplementation. Serum concentrations of insulin-like growth factor I increased in the milk group compared with the control group (35% v 25%, P = 0.02). CONCLUSION: Increased milk consumption significantly enhances bone mineral acquisition in adolescent girls and could favourably modify attainment of peak bone mass.     

Effect of melatonin on bone metabolism in ovariectomized rats.

To assess the effect of pharmacological dose of melatonin on bone metabolism in ovariectomized rats, urinary deoxypyridinoline (a marker of bone resorption) and calcium excretion, circulating levels of calcium, phosphorus and bone alkaline phosphatase activity (a marker of bone formation), and bone mineral density (BMD), mineral content (BMC) and bone area (BA) of total body, were measured in adult rats for up to 60 days after surgery. Rats received melatonin in the drinking water (25 microg/ml water) or drinking water alone. Urinary deoxypyridinoline increased significantly after ovariectomy by 51% (30 days after surgery) and by 47% (60 days after surgery). The increase in urinary deoxypyridinoline found 30 days after ovariectomy was not observed in melatonin-treated rats. Urinary calcium concentration was similar in the 4 experimental groups studied, as was the circulating calcium concentration at every time interval examined. Fifteen days after surgery, a significant increase in serum phosphorus and bone alkaline phosphatase levels occurred in ovariectomized rats receiving melatonin as compared to their controls. Sixty days after surgery BMD, BMC and BA decreased significantly in ovariectomized rats, an effect not modified by melatonin. Serum estradiol decreased significantly by 30 days after ovariectomy to attain values close to the limit of detection of the assay by 60 days after ovariectomy. The results support the conclusion that a pharmacological amount of melatonin modifies bone remodeling after ovariectomy and that the effect may need adequate concentrations of estradiol.     

32k Da protein improve ovariectomy-induced bone loss in rats

The objective of the present study was to systematically explore the effects of 32K Da protein (32KP) on postmenopausal osteoporosis. Eighty 3-mo-old female Sprague-Dawley rats were employed and randomly divided into one sham-operated group (SHAM) and five ovariectomy (OVX) subgroups as OVX (control), OVX with 17-ethinylestradiol (E2, 25 g/kg/day), OVX with 32KP of graded doses (50, 50, or 150 mg/kg/day). 32KP or E2 diet was fed on week 4 after operation, for 16 weeks. Bone mass, bone turnover and strength were evaluated by dual-energy X-ray absorptiometry (DEXA), biochemical markers and three-point bending test, respectively. Femur marrow cavity was observed by light microscopy via hematoxylin-eosin staining. It is observed that different dosage treatment of 32KP increased the body weight and prevented the loss of bone mass induced by OVX. The prevention effect against bone loss was presumably due to the altering of the rate of bone remodeling. The bone mineral density and bone calcium content in OVX rats were lower than that in the control group, suggesting that 32KP was able to prevent significant bone loss. In addition, the data from three point bending test and femur sections showed that 32KP treatment enhanced bone strength and reduced the marrow cavity of the femur in OVX rats. In the serum and urine assay, 32KP decreased urinary deoxypyridinoline and calcium concentrations; however, serum alkaline phosphatase activities were not inhibited. It suggested that amelioration of bone loss was changed via inhibition of bone reabsorption. Our findings indicated that 32KP might be a potential alternative drug for the prevention and treatment of postmenopausal osteoporosis.     

Bone loss in the ovariectomized baboon Papio ursinus: densitometry, histomorphometry and biochemistry

To develop a non-human primate model of systemic bone loss after ovariectomy, 24 ovariectomized (OVX) and eight control (non-OVX) female baboons Papio ursinus were investigated over a period of 48 months using bone mineral density (BMD), iliac crest bone histomorphometry, bone turnover markers, and variables of calcium metabolism. Lumbar spine (L1-L4) BMD measured by dual energy X-ray absorptiometry (DXA) decreased in OVX animals in the first 12 months (-7.6%) and showed a slow trend towards recovery after 24 months. Controls showed a slow increase in spinal BMD over 4 years (+9.7%). Total hip BMD decreased slowly up to 48 months in all animals (OVX -12.6%versus controls -10%); this indicated that OVX had a limited effect on total hip BMD. Forearm BMD did not change. The significant decrease in trabecular bone volume (TBV) of the iliac crest from baseline to 12 months was followed by some recovery. Microarchitectural deterioration of trabecular bone in OVX animals was demonstrated by a decline in trabecular number and an increase in trabecular spacing. These changes were also evident on sections of whole vertebrae, proximal femora and iliac crests. Changes in iliac TBV reflected spinal but not hip BMD changes in the OVX animals. Static and dynamic histomorphometric variables indicated that bone turnover was increased for 36 months following OVX. Controls showed no changes in histomorphometric variables. Bone specific alkaline phosphatase (ALPs) in OVX animals remained elevated throughout the study; osteocalcin (OC) was significantly elevated only at 6 and 12 months, and deoxypyridinoline (Pyr-D) was elevated at 12 months but declined after 24 months. ALPs was thus more sensitive to the long-term effects of OVX than were OC or Pyr-D. Controls showed no changes in bone turnover markers. This study showed consistent deleterious changes in lumbar BMD, bone histomorphometry with microarchitectural deterioration together with altered biochemical markers of bone turnover in the first 12 months after OVX. Since these changes resemble those in post-menopausal women, the non-human primate Papio ursinus is suitable for the study of bone loss in post-menopausal women.     

Serum BAP as the clinically useful marker for predicting BMD reduction in diabetic hemodialysis patients with low PTH

With decrease of serum PTH in hemodialysis (HD) patients, other factors besides parathyroid hormone (PTH) become important in regulating bone metabolism. We investigated which serum bone metabolic marker is the best to predict the bone mineral density (BMD) reduction in HD patients with serum PTH<180 pg/ml. The bone formation markers, bone alkaline phosphatase (BAP), intact osteocalcin (OC), and N-terminal propeptide of type I collagen (PINP), and the bone resorption markers, deoxypyridinoline (DPD), pyridinoline (PYD), and beta-crossLaps (beta-CTx) were measured in serum from 137 HD patients. BMD of all patients was measured twice, approximately 1.5 years before and 1.5 years after measurement of their markers of bone metabolism. In all 137 HD patients, serum BAP was the only marker significantly higher in those with BMD reduction than in those without. In 42 diabetes mellitus (DM) HD patients with serum PTH<180 pg/ml, hypothetically low bone turnover state, serum BAP was again the only marker to discriminate those with BMD reduction from those without. At serum PTH<60 pg/ml, serum BAP retained tendency toward higher value. These findings suggest that serum BAP might be the most sensitive to identify small changes of bone metabolism in low bone turnover state. Retrospective study confirmed the usefulness of serum BAP in clinical practice by significantly higher values in those with bone loss at PTH<180 pg/ml even in under routine sample handling. In conclusion, serum BAP is a clinically useful bone formation marker to predict the BMD reduction in DM HD patients with low level of PTH.     

大豆异黄酮对去卵巢大鼠骨密度及骨代谢影响的实验研究

目的 探讨大豆异黄酮对去卵巢大鼠骨丢失的防治作用及其作用机理。方法 选用卵巢切除大鼠所诱发的骨质疏松模型,给与大豆异黄酮治疗。三个月后测定大鼠骨密度及骨代谢相关生化指标。结果 大豆异黄酮可提高卵巢切除大鼠的骨密度及血清雌激素水平,降低尿钙（Ca),尿磷（P）及尿羟脯氨酸（HOP）的排泄,同时降低血清总碱性磷酸酶（ALP）,骨碱性磷酸酶（BALP）,及抗酒石酸酸性磷酸酶（TRACP）的活性,还可使血清骨钙素（BGP）的浓度降低,促使卵巢切除大鼠子宫的相对重量增加,其作用与剂量相关。结论 小剂量大豆异黄酮有类似雌激素样作用,可有效防治卵巢切除大鼠的骨量丢失,其作用机制可能是通过降低骨转换率实现的。     

Bone and Gastric Bypass Surgery: Effects of Dietary Calcium and Vitamin D

Objective:To examine bone mass and metabolism in women who had previously undergone Roux‐en‐Y gastric bypass (RYGB) and determine the effect of supplementation with calcium (Ca) and vitamin D. Research Methods and Procedures: Bone mineral density and bone mineral content (BMC) were examined in 44 RYGB women (≥3 years post‐surgery; 31% weight loss; BMI, 34 kg/m²) and compared with age‐ and weight‐matched control (CNT) women (n = 65). In a separate analysis, RYGB women who presented with low bone mass (n = 13) were supplemented to a total 1.2 g Ca/d and 8 μg vitamin D/d over 6 months and compared with an unsupplemented CNT group (n = 13). Bone mass and turnover and serum parathyroid hormone (PTH) and 25‐hydroxyvitamin D were measured. Results:Bone mass did not differ between premenopausal RYGB and CNT women (42 ± 5 years), whereas postmenopausal RYGB women (55 ± 7 years) had higher bone mineral density and BMC at the lumbar spine and lower BMC at the femoral neck. Before and after dietary supplementation, bone mass was similar, and serum PTH and markers of bone resorption were higher (p < 0.001) in RYGB compared with CNT women and did not change significantly after supplementation. Discussion: Postmenopausal RYGB women show evidence of secondary hyperparathyroidism, elevated bone resorption, and patterns of bone loss (reduced femoral neck and higher lumbar spine) similar to other subjects with hyperparathyroidism. Although a modest increase in Ca or vitamin D does not suppress PTH or bone resorption, it is possible that greater dietary supplementation may be beneficial.     

Effects of growth hormone replacement therapy on bone markers and bone mineral density in growth hormone-deficient adults

During the 1990s, interest in the effects of growth hormone deficiency (GHD) in adults increased, and several studies were performed to evaluate the effects of growth hormone (GH) substitution therapy in these patients. Because adults with GHD have reduced bone mineral density (BMD) and an increased risk of fractures, the effects of GH replacement therapy on bone metabolism have been evaluated in long-term studies. A universal finding is that the serum and urinary levels of biochemical bone markers increase during GH substitution therapy, and these increases are dose dependent. After years of GH substitution therapy, the levels of biochemical bone markers remain elevated, according to some studies, whereas other studies report that these levels return to baseline. BMD of the spine, hip and forearm increase after 18-24 months of treatment. Bone mineral content (BMC) increases to a greater extent than BMD, because the areal projection of bone also increases. This difference could be caused by increased periosteal bone formation, but a measurement artefact resulting from the use of dual-energy X-ray absorptiometry cannot be excluded as a possible explanation. One study of GH-deficient adults found that, after 33 months of GH treatment, BMD and BMC increased to a greater extent in men with GHD than in women. There is also a gender difference in the increases in serum levels of insulin-like growth factor I and biochemical bone markers during GH treatment. The reason for these findings is unknown, and the role of sex steroids in determining the response to GH therapy remains to be fully elucidated.