Osteocalcin and bone alkaline phosphatase in the serum of women with liver disease

To identify the types of liver disease in which osteopenia is a prominent feature and to understand the mechanisms of bone loss, bone mineral density was measured in the lumbar spine and hip, bone alkaline phosphatase, osteocalcin, and biochemical markers of calcium homeostasis were measured in 42 women, aged 33 to 52, with chronic liver disease and in 299 healthy women of similar age. In control women, bone alkaline phosphatase and osteocalcin correlated negatively with bone density at all sites (p less than 0.05). In women with liver disease, osteocalcin correlated negatively with bone density in the lumbar spine (p less than 0.007), whereas bone alkaline phosphatase did not correlate with bone density at any site. Bone alkaline phosphatase correlated positively with osteocalcin in control women (p = 0.001) and negatively with osteocalcin in women with liver disease (p = 0.03). Serum bone alkaline phosphatase in women with liver disease was increased significantly over serum bone alkaline phosphatase of control women, probably because of decreased clearance owing to defective function or decreased numbers of hepatic asialoglycoprotein receptors. Bone density was lower in the lumbar spines and hips of women with primary sclerosing cholangitis, primary biliary cirrhosis, and chronic active hepatitis or fibrosis without cirrhosis than in the lumbar spine and hips of control women. However, the differences were not significant, possibly because of the small sample size. It is concluded that, in liver disease, osteocalcin is a more reliable marker of osteoblastic function than bone alkaline phosphatase. Although our results show that bone density may decrease in women with cholestatic liver disease, larger studies are needed to determine the degree of osteopenia.     

Relationship of osteocalcin and matrix Gla protein gene polymorphisms to serum osteocalcin levels and bone mineral density in postmenopausal Korean women

OBJECTIVE: To investigate the relationship of osteocalcin and matrix Gla protein (MGP) gene polymorphisms to serum osteocalcin levels, and bone mineral density (BMD) in postmenopausal Korean women. DESIGN: The osteocalcin gene Hind III and MGP gene cytosine-adenine polymorphisms were analyzed in 267 postmenopausal Korean women. Serum osteocalcin, bone alkaline phosphatase, C-telopeptide of type I collagen, and BMD at the lumbar spine and femoral neck were measured. RESULTS: No significant differences in BMD of the lumbar spine and femoral neck were observed across MGP genotypes, whereas a significant lower BMD at the lumbar spine (but not at the femoral neck) was observed in women with the (h) allele (lower case 'h' signifies the presence of the Hind III site) in a dose-response manner. Serum osteocalcin levels among bone turnover markers studied were significantly higher in women without the 210-bp MGP (cytosine-adenine) allele, or with the osteocalcin hh genotype. CONCLUSIONS: The osteocalcin gene Hind III polymorphism is a genetic factor that is associated with BMD of the lumbar spine in Korean women, and Gla gene polymorphisms are associated with higher osteocalcin levels.     

Effects of inhaled budesonide on serum markers of bone metabolism in children with asthma.

The effects of inhaled glucocorticoids on serum markers of bone formation were evaluated in asthmatic children. Serum total alkaline phosphatase (AP), bone alkaline phosphatase (BAP), osteocalcin, and the novel marker of bone formation, carboxypropeptide of type I procollagen (PICP), were measured. In the cross-sectional part, long-term glucocorticoid users were compared with sodium cromoglycate (SCG) users. In the boys (n = 16), but not in the girls (n = 11), PICP was significantly lower in the glucocorticoid users than in the SCG users. PICP correlated positively with BAP (n = 54; groups combined, r = 0.29, p < 0.05). In the longitudinal part, the effects of inhaled budesonide or SCG, both used for the first time, were evaluated before and after 1 and 5 months of treatment. The budesonide dose was 800 micrograms/m2/day for 1 month and thereafter half of that. The SCG dose was 30 mg/day throughout the study. Only during budesonide use did osteocalcin and PICP decrease, the median osteocalcin by 8% at 1 month (p < 0.05) and by 6% at 5 months (n = 15), and PICP by 5% at 1 month (p < 0.05) and by 28% at 5 months (n = 7, p < 0.01). AP and BAP did not change significantly. Decreased PICP suggests decreased bone formation rate. PICP might be clinically useful as a marker of early adverse effects of glucocorticoids on bone.     

Evaluation of bone metabolism and bone mass in patients with type-2 diabetes mellitus

The objectives of this study were to determine whether type-2 diabetes was associated with a higher bone mineral density (BMD) in men and women and to evaluate the differences in mineral metabolism between diabetic and normal subjects by using biochemical bone turnover markers. In this study, 52 patients (37 females/15 males) aged 41-64 with type-2 diabetes mellitus and 48 nondiabetic control subjects (34 females/14 males) were evaluated. In men, BMD was significantly higher in diabetics at the forearm (p <0.05), whereas in women tended to be higher at the hip (p=0.002). Serum osteocalcin (p<0.0001), bone alkaline phosphatase (BAP) (p<0.05) and carboxyterminal telopeptide (CTx) (p<0.05) were higher in the control group than in diabetics. In men, serum osteocalcin (p<0.05) and CTx (p<0.005) and, in women, serum osteocalcin (p<0.0001) and BAP (p<0.05) were lower in diabetic subjects. In conclusion, our findings suggest that although bone formation is decreased in type-2 diabetes, diabetic patients are not susceptible to bone resorption. This low bone turnover can slow the rate of bone loss and cause a higher bone density than expected for their age.     

Seasonal differences in biochemical parameters of bone remodelling.

AIMS: To compare bone remodelling parameters in late autumn and early spring in 20 post-menopausal women. METHODS: The parameters measured were serum osteocalcin and its apparent degree of carboxylation (measured by hydroxyapatite binding), total and bone specific alkaline phosphatase and urinary bone resorption markers, (pyridinoline and deoxypyridinoline). RESULTS: Serum osteocalcin concentrations were lower in autumn than in spring but the degree of carboxylation was similar. Total and bone specific alkaline phosphatase activities in serum were higher in autumn than in spring. These results support previous observations. However, notable and previously unreported changes in urinary bone resorption markers were observed. Pyridinoline concentrations were lower and deoxypyridinoline higher in autumn compared with spring. The ratio of pyridinoline:deoxypyridinoline was therefore very different between the seasons. CONCLUSIONS: The results clearly demonstrate that seasonal changes in these variables of bone remodelling must be taken into consideration when designing, reporting or analysing studies of bone metabolism in vivo.     

Cathepsin K predicts femoral neck bone mineral density change in nonosteoporotic peri- and early postmenopausal women

OBJECTIVE: Cathepsin K is a cysteine protease that plays an essential role in organic bone matrix degradation. The aim of our study was to seek correlation of serum cathepsin K levels and a change in bone mineral density (BMD) over a 3-year period in a population of healthy nonosteoporotic women. The secondary end points were the correlations of serum cathepsin K with cross-sectional BMD and with other serum bone turnover markers and age. DESIGN: In 43 healthy women aged 42 to 57 years, blood samples for determination of cathepsin K, osteocalcin, bone alkaline phosphatase, C-terminal cross-linking telopeptide of type I collagen, osteoprotegerin, and nuclear factor kappaB ligand were collected at the time of the first BMD measurement. BMD measurements were repeated after 3 years. RESULTS: We found a moderate negative correlation of serum cathepsin K levels with change in femoral neck BMD, but none with change in spinal BMD. There were no significant correlations between cross-sectional BMD of the spine or femoral neck and serum levels of cathepsin K. Serum levels of cathepsin K were not significantly correlated with any bone turnover markers studied or with age. CONCLUSIONS: Serum cathepsin K does not seem to represent a surrogate for bone turnover markers used at present, but it might be useful as a predictor of cortical bone loss.     

Serum gamma-glutamyltransferase and alkaline phosphatase in rheumatoid arthritis.

Serum gamma-glutamyltransferase (GGT) and alkaline phosphatase (AP) were assayed in 98 consecutive patients with rheumatoid arthritis. Twenty-three patients had increased GGT activities and 45 an increased AP activity. Twelve patients showed an increase in both enzyme activities and AP isoenzyme studies were performed on seven of this group. In three subjects an increase in the bone isoenzyme was observed and in three others the increase in activity was attributed to the liver isoenzyme. The remaining patient, who probably suffered from coexistent primary biliary cirrhosis, showed an increase in both bone and liver isoenzymes. The liver involvement, suggested by the alkaline phosphatase isoenzyme results, was largely confirmed by the butanol extraction of GGT. The changes in these enzymes in this small series could not be related definitely to drug therapy. It is concluded that though increases in GGT and AP are common in rheumatoid arthritis, this does not necessarily indicate hepatic involvement. Further isoenzyme studies are needed to define the extent to which organs other than the liver bring about increases in these serum enzymes in rheumatoid disease.     

绝经后妇女骨代谢过程中血清基质金属蛋白酶3和骨桥蛋白的变化

背景：骨桥蛋白和基质金属蛋白酶3具有高度的亲和力,此二者的表达可能与骨代谢有关。 目的：观察绝经后妇女血清基质金属蛋白酶3和骨桥蛋白水平,并观察其与骨保护蛋白、骨保护蛋白配体及骨代谢指标的关系。 方法：将120名绝经后妇女分为骨密度正常组、低骨量组和骨质疏松组3 组,对其血清基质金属蛋白酶3、骨桥蛋白、骨保护蛋白、骨保护蛋白配体及骨碱性磷酸酶、骨钙素、Ⅰ型胶原交联C端肽和尿Ⅰ型胶原交联N端肽进行测定,计算骨桥蛋白/基质金属蛋白酶3比值。 结果与结论：骨质疏松组中血清骨桥蛋白和基质金属蛋白酶3的水平高于正常组(P < 0.05)。绝经后妇女血清基质金属蛋白酶3、骨桥蛋白和骨桥蛋白/基质金属蛋白酶3比值与血清骨保护蛋白配体、骨碱性磷酸酶和骨钙素水平呈明显负相关 (P < 0.05),与骨保护蛋白、尿尿Ⅰ型胶原交联N端肽/肌酐比值呈明显正相关性(P < 0.05)。骨质疏松组中血清基质金属蛋白酶3、骨桥蛋白和骨桥蛋白/基质金属蛋白酶3比值与血清骨保护蛋白配体、骨碱性磷酸酶和骨钙素水平呈明显负相关 (P < 0.05),与骨保护蛋白、尿尿Ⅰ型胶原交联N端肽/肌酐水平比值存在明显正相关性(P < 0.05)。提示绝经后妇女血清骨桥蛋白水平和骨桥蛋白/基质金属蛋白酶3比值升高与绝经后骨质疏松症伴随骨代谢转换过程增快有关。     

Effect of beclomethasone dipropionate nasal aerosol on serum markers of bone metabolism in children with seasonal allergic rhinitis

Thirty-nine children with grass pollen hay fever were randomly treated with nasal inhaled beclomethasone dipropionate (BDP) 200 or 400 microg/day or sodium cromoglycate (SCG) 30 mg/day for 2 months during the pollen season. Serum osteocalcin (OC), parathyroid hormone (PTH), total alkaline phosphatase (AP), bone alkaline phosphatase (BAP) and type I collagen telopeptide (ICTP) were measured immediately before, 1 and 2 months after treatment and 1 week after stopping the therapy. No significant changes in OC, PTH, AP, BAP and ICTP serum level occurred within each group. Minor and probably clinically insignificant between group differences were occasionally found. Our study shows that BDP nasal spray has no significant effect on common markers of bone metabolism.     

Change in serum undercarboxylated osteocalcin concentration in bilaterally oophorectomized women

Objective

We investigated changes in serum undercarboxylated osteocalcin (ucOC) concentrations, bone turnover markers and spine bone mineral density (BMD) in women who had undergone bilateral oophorectomy during the premenopausal period.

Methods

The study population comprised 141 bilaterally oophorectomized and 32 premenopausal women for a cross-sectional study. The longitudinal study consisted of 21 bilaterally oophorectomized women. Serum ucOC concentration, serum concentrations of intact osteocalcin (OC) and bone-specific alkaline phosphatase (BAP) as bone formation markers, urine N-telopeptide (NTx) concentration as a bone resorption marker and serum parathyroid hormone (PTH) concentration were measured.

Results

Serum concentration of ucOC in women at 1 month after bilateral oophorectomy was significantly (p < 0.05) higher than that in premenopausal women and the high level was sustained after surgical menopause. On the other hand, serum OC concentration at 1 month after surgical menopause was not different from that in premenopausal women. In the longitudinal study, serum ucOC concentration at 1 month after surgical menopause was significantly (p < 0.05) increased compared to that before bilateral oophorectomy, while serum OC concentrations before and at 1 month after surgical menopause were not significantly different.

Conclusion

The results of this study showed that serum ucOC concentration rapidly increases in women after bilateral oophorectomy and that change in serum ucOC concentration after surgical menopause is different from change in serum OC concentration.     

Correlation of Undercarboxylated Osteocalcin (ucOC) Concentration and Bone Density with Age in Healthy Korean Women

Uncarboxylated osteocalcin (ucOC) is important in evaluating vitamin K status and it is inversely associated with bone mineral density (BMD). We studied the correlationship between ucOC and BMD in healthy Korean women. This study recruited 337 healthy women between ages 20-70 were recruited. Serum ucOC, calcium, alkaline phosphatase, body mass index (BMI), and BMD were measured and compared. Mean BMI was lowest (20.3±1.9 kg/m²) in the 20 yr old group and highest (24.8±2.6 kg/m²) in the 60 yr old group. Women age 20-70 yr old had ucOC inversely related to BMD independent of other factors that may influence BMD. Serum ucOC concentration and BMD of lumbar spine showed a significant inverse relationship. Serum mean alkaline phosphatase was lowest (122±30 IU/L) in the age 30 group and highest (190.3±55.8 IU/L) in the age 60 group. Serum ucOC was inversely associated with BMI, and positively associated with alkaline phosphatase. Uncarboxylated osteocalcin (ucOC) was inversely associated with spinal BMD in healthy Korean women. Serum mean ucOC was highest in the age 20 group, followed by age 50 group, which may indicate vitamin K insufficiency could be related to high bone turnover in these groups. These results suggest that vitamin K supplement may be considered to help both bone growth and bone loss during these periods.     

二次骨折风险评价：老年女性髋部骨折后6-12个月骨密度及骨代谢变化

背景：国内外文献中关于骨折后骨代谢指标及骨密度变化量的前瞻性研究在20世纪60年代就开始有文献报道,但主要集中于胫腓骨和踝关节骨折患者,且样本量较低。 目的：观察老年女性髋部骨折愈合后(伤后6-12个月)骨密度及骨代谢指标的变化情况,并分析其相关性。 方法：选择2011年5月至2013年7月北京航天总医院骨科收治的老年女性髋部骨折患者48例,制定随访标准进行L1-4、患侧、健侧髋部骨密度测量及骨代谢指标骨碱性磷酸酶、骨钙素、Ⅰ型胶原交联C末端肽、血清抗酒石酸酸性磷酸酶5b水平测定,并行骨折愈合后患侧全髋部骨密度与血清骨代谢指标的多元线性回归分析。 结果与结论：患者骨折愈合后,患髋及腰椎骨密度显著低于基线值,健髋部位骨密度与基线值差异无显著性意义。患者在伤后6个月,即骨折完全愈合时,骨代谢指标骨碱性磷酸酶、骨钙素、Ⅰ型胶原交联C末端肽、血清抗酒石酸酸性磷酸酶5b水平均显著高于基线值(P < 0.05)。患者在伤后12个月,即骨折完全愈合6个月,骨钙素水平显著高于基线值,其余骨代谢指标与基线值差异无显著性意义。骨折达到临床及影像学愈合后,血清骨钙素水平的改变量与患髋骨密度改变量的偏回归系数最大。提示骨折达到临床愈合后,骨钙素血清水平对于评估骨密度回升速度具有较高价值。骨折愈合后监测相应的骨代谢指标可以提高判断骨密度变化的准确性,以降低罹患二次骨折的风险。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程全文链接：     

Decreased serum osteocalcin levels in patients with postmenopausal osteoporosis.

Osteocalcin is a 49 amino acid non collagenous bone matrix protein which is synthesized by the osteoblasts. The serum levels of osteocalcin have been found to be a specific biochemical parameter of bone formation. We determined the serum levels of osteocalcin, parathyroid hormone, calcitonin and alkaline phosphatase as well as the 2 hour fasting hydroxyproline excretion in 26 patients with postmenopausal osteoporosis and in 24 postmenopausal control subjects. Serum levels of osteocalcin were significantly lower in the patients with postmenopausal osteoporosis than in the control subjects (p less than 0.002). In contrast, serum levels of parathyroid hormone, calcitonin, alkaline phosphatase and the 2 hour hydroxyproline excretion in the patients with postmenopausal osteoporosis and the control subjects were not statistically different. Our data give evidence of a decreased bone formation in patients with postmenopausal osteoporosis.     

Serum lipid concentrations change with serum alkaline phosphatase activity during pregnancy

To investigate the relationship between serum lipids and alkaline phosphatase during normal pregnancy, we measured triglyceride, total cholesterol, HDL-cholesterol, and LDL-cholesterol concentrations and alkaline phosphatase activity in serum samples from 546 apparently healthy pregnant, postpartum, and nonpregnant women. Serum HDL-cholesterol levels did not change significantly during pregnancy, but serum triglyceride, total cholesterol, LDL-cholesterol, and alkaline phosphatase levels increased gradually as pregnancy proceeded, reached maximum values in the third trimester, and returned to nonpregnant levels by 20-24 wk postpartum. The serum alkaline phosphatase activity averaged 2.1-fold higher in the late third trimester than in the first trimester; the serum triglyceride concentration averaged 2.3-fold higher in the late third trimester than in the first trimester. Compared to the peak values during pregnancy, serum alkaline phosphatase activity averaged 45% lower and serum triglyceride level averaged 47% lower at 12-16 wk postpartum. The serum alkaline phosphatase activity was correlated with the serum concentrations of total cholesterol (r = 0.68, p < 0.01) and triglyceride (r = 0.71, p < 0.01). In short, this study shows that serum triglyceride and total cholesterol levels change in parallel with serum alkaline phosphatase activity during and after normal pregnancy.     

Calcium homeostasis, bone metabolism and safety aspects during long-term treatment with a GnRH agonist.

Thirty-five women with symptomatic fibroids were treated with monthly injections of 3.2 mg microcapsulated D-Trp-6-LHRH for 6 months. During treatment serum 17 beta-oestradiol levels decreased, falling to castration levels associated with a reduction in the volume of the fibroids. In 16 patients a complete calcium homeostasis and bone metabolism work-up was carried out during treatment and subsequently for a 6-month follow-up period. Bone mineral content (BMC) and Compton bone densitometry readings remained unchanged. There were significant increases in serum calcium phosphate and alkaline phosphatase concentrations. A slight although not significant increase was observed in osteocalcin and parathyroid hormone (PTH) serum levels. Serum 1,25(OH)2D3 values decreased significantly after 3 months of treatment. Urinary hydroxyproline/creatinine and calcium/creatinine ratios as well as 24-h urinary calcium values increased significantly during the treatment period but decreased rapidly to pretreatment values after 3 months in the follow-up period. The endocrine changes induced by the GnRH-agonist treatment were associated with reversible biochemical signs of increased bone turnover and no significant changes in bone mass, suggesting that the treatment can be administered safely for a period of 6 months in patients with oestrogen-dependent diseases.     

Value of the study of total alkaline phosphatases and bone isoenzyme in a population of subjects with osteoporosis]

The authors have compared the values of total and bone serum alkaline phosphatases in an osteoporotic population and a control group. The total activity of alkaline phosphatases was determined by a kinetic method at 30 degrees C and alkaline phosphatase isoenzymes were separated by agarose gel electrophoresis in presence or absence of wheat germ lectin. The authors have confirmed reported data concerning the physiological variations of alkaline phosphatases in the control group; they have therefore divided each group in several sub-populations according to age and sex in order to obtain accurate comparisons. Mean values of total and bone alkaline phosphatases were greater in the osteoporotic population than in the control group regardless of age or sex. Nevertheless, significant differences were obtained only with 50 to 75 year-old subjects (men or women) for total alkaline phosphatases and with 50 to 75 year-old women for bone alkaline phosphatase.     

Evaluation of the antiosteoporotic potential of Tinospora cordifolia in female rats

The available courses of therapy to osteoporosis in menopausal women are limited by several side effects generated. A need therefore arises to explore herbal alternatives that are effective and safe. OBJECTIVE: Present animal studies were conducted to investigate the potential of Tinospora cordifolia (TC) ethanolic stem extract as an antiosteoporotic agent. METHODS: Three-month-old female Sprague-Dawley rats were either ovariectomized (ovx) or sham operated and treated with vehicle (benzyl benzoate:castor oil; 1:4), E(2) (1 microg/day) or TC (10, 50, 100 mg/kg b.wt) subcutaneously for 4 weeks. At the end of experiment bone mineral density of tibiae was measured by quantitative computer tomography. Serum was analyzed for the activity of alkaline phosphatase and levels of osteocalcin, cross-laps and lipids. Uterus and mammary gland were processed for histological studies. RESULTS: Ovx rats treated with TC (10 mg/kg b.wt) showed an osteoprotective effect as the bone loss in tibiae was slower than ovx controls. Serum osteocalcin and cross-laps levels were significantly reduced. All the above effects of TC were much milder than those produced by E(2). Alkaline phosphatase activity was higher in TC treatment groups. Total cholesterol and LDL levels remained unaltered but HDL levels were significantly lowered with TC (50 mg/kg b.wt) treatment. Uterus and mammary gland showed no signs of proliferation after treatment with TC extract. CONCLUSION: TC extract showed estrogen like effects in bone but not in reproductive organs like uterus and mammary gland. Thus, this study demonstrates that extract of T. cordifolia has the potential for being used as antiosteoporotic agent.     

Soy isoflavones for osteoporosis: an evidence-based approach

Effects of soy isoflavones on osteoporosis remain unclear. This review aimed to clarify the effect of soy isoflavones on bone mineral density (BMD) and turnover markers in menopausal women. PubMed and the Cochrane Library were searched in July 2011 for relevant meta-analyses of randomized controlled trials evaluating effects of soy isoflavones on BMD and bone turnover markers. Three meta-analyses evaluated the effects of soy isoflavones on lumbar spine, total hip, femoral neck, and trochanter BMD. Soy isoflavones significantly improved lumbar spine BMD in a moderate manner, but did not affect total hip, femoral neck, and trochanter BMD in menopausal women. Ingestion of soy isoflavones for six months appeared to be enough to exert a beneficial effect on lumbar spine BMD. Two meta-analyses evaluated the effects of soy isoflavones on a bone resorption marker (urine deoxypyridinoline) and two formation markers (serum alkaline phosphatase and osteocalcin). Soy isoflavones significantly decreased urine deoxypyridinoline in a moderate manner, but did not affect serum alkaline phosphatase and osteocalcin in menopausal women. Soy isoflavones may prevent postmenopausal osteoporosis and improve bone strength thus decreasing risk of fracture in menopausal women by increasing lumbar spine BMD and decreasing bone resorption marker urine deoxypyridinoline. Further studies are needed to address factors affecting the magnitude of the beneficial effects of soy isoflavones and to assess the possible interactions between soy isoflavones and anti-osteoporosis drugs, and to verify effects on BMD of other skeletal sites and other bone turnover markers.     

Serum osteocalcin levels in primary hyperparathyroidism

Summary The serum levels of osteocalcin, a 49-amino-acid bone-matrix protein, have been found to be a specific biochemical parameter of bone formation. The aim of our study was to compare the sensitivity of serum osteocalcin levels with that of alkaline phosphatase in the evaluation of patients with primary hyperparathyroidism. In 40 patients with biochemically and histologically confirmed primary hyperparathyroidism, the serum levels of osteocalcin, intact parathyroid hormone, alkaline phosphatase, calcium, phosphorus, and creatinine were determined preoperatively. The serum levels of osteocalcin were elevated in 22 patients (55%), whereas the serum levels of alkaline phosphatase were increased in 18 patients (45%). In 10 patients (25%) the serum levels of osteocalcin, but not those of alkaline phosphatase, were increased, whereas in six patients the activity of alkaline phosphatase was high, but the serum osteocalcin levels were normal. When the biochemical data of the patients with increased serum osteocalcin levels were compared with those of the patients with serum osteocalcin levels within the normal range, the serum levels of intact parathyroid hormone and alkaline phosphatase were significantly increased in the group of patients with elevated serum osteocalcin levels. Our data indicate that serum osteocalcin levels might be a clinically useful additional parameter in the evaluation of patients with primary hyperparathyroidism.     

Increased bone remodeling in first-episode major depressive disorder

OBJECTIVE: Bone mineral density is decreased in patients with depressive disorder. This study evaluated biochemical bone remodeling markers in patients having their first depressive episode who had not taken psychotropic medications to evaluate possible pathogenic mechanisms implicated in the loss of bone mineral density in early states of this illness. METHODS: Serum osteocalcin, parathyroid hormone, bone alkaline phosphatase, telopeptide, collagen type I C-terminal propeptide, cross-laps, and 25-hydroxyvitamin D levels were measured in 19 depressive patients and 19 age-matched healthy women. In addition, serum cortisol and interleukin-6 were determined. Patients were assessed with the Schedules for Clinical Assessment in Neuropsychiatry interview and met criteria for a single depressive episode. RESULTS: Depressed patients had increased levels of osteocalcin (p = .003), an osteoblastic marker; telopeptide (p = .01), an osteoclastic marker; and cross-laps (p = .000), another osteoclastic marker. Parathyroid hormone was lower in patients (p = .02), whereas the rest of the markers were comparable between patients and healthy control subjects. Serum cortisol was higher in depressed patients than in control subjects (p = .003), but cortisolemia and interleukin-6 did not show any relationship with bone markers in patients. Clinical severity of the illness and weight loss due to depression in patients did not correlate with bone remodeling markers. CONCLUSIONS: These data suggest that an increase in bone remodeling not due to vitamin D deficiency induces a release of calcium from bone and inhibition of parathyroid hormone secretion.