Biochemical Markers Of Bone Metabolism Research Articles

Effects of Arzoxifene on Bone Mineral Density and Endometrium in Postmenopausal Women with Normal or Low Bone Mass

Arzoxifene, a benzothiophene estrogen agonist/antagonist, is being developed for prevention and treatment of osteoporosis and for risk reduction of invasive breast cancer in postmenopausal women. The effects of arzoxifene 20 mg/d on bone mineral density (BMD), uterine safety, and overall safety were studied in the FOUNDATION study, a 2-yr randomized, placebo-controlled trial including 331 postmenopausal women with normal to low bone mass. Compared to placebo, arzoxifene significantly increased lumbar spine (+2.9%) and total hip (+2.2%) BMD. Arzoxifene decreased biochemical markers of bone metabolism compared to placebo. Changes in breast density were neutral or slightly decreased in the arzoxifene vs. placebo group. There was no evidence of endometrial hyperplasia or carcinoma in the arzoxifene group as assessed by central review of baseline and follow-up endometrial biopsies. There was no significant change between the groups in endometrial thickness assessed by transvaginal ultrasound. The incidence of uterine polyps and vaginal bleeding was not significantly different between the groups. Vulvovaginal mycotic infection was the only adverse event significantly increased in the arzoxifene vs. placebo group. Hot flushes were not significantly different between the groups. In postmenopausal women with normal to low bone mass, arzoxifene 20 mg/d increased BMD at the spine and hip and had a neutral effect on the uterus and endometrium.

Bone turnover and type I collagen C-telopeptide isomerization in adult osteogenesis imperfecta: Associations with collagen gene mutations

Introduction Increased bone fragility in osteogenesis imperfecta (OI) is not totally accounted for by decreased bone mineral density (BMD), and alterations of type I collagen (Col I) are believed to play a role. Newly synthesized Col I comprises non isomerized C-telopeptide (αCTX), but with bone matrix maturation αCTX is converted to its isomerized β form (βCTX). Urinary α/βCTX ratio has been proposed to reflect collagen maturation. We investigated changes in bone turnover and Col I isomerization in adult patients with OI and their relationship with Col I gene mutations. Patients and methods Sixty four adult patients [25 women, 39 men mean age (SD): 36.2 (11.6) years] with OI participating in a randomized study and 64 healthy controls of similar age and gender distribution were investigated. In patients with OI and controls, we measured the following biochemical markers of bone metabolism: serum type I collagen N-propeptide (PINP) an index of Col I synthesis, osteocalcin a marker of osteoblastic activity, urinary Col I helical peptide, a marker reflecting the degradation of the helical portion of Col I, urinary αCTX and urinary and serum βCTX. Based on the putative functional effects of Col I gene mutations which were identified in 56 OI subjects, patients were divided in those with haploinsufficiency ( n = 29), patients presenting with helical domain alterations ( n = 17) and others ( n = 10). Results Compared to healthy controls, patients with OI had decreased levels of PINP (− 22.7%, p < 0.0001), increased osteocalcin (+ 73%, p < 0.0001) and increased Col I helical peptide (+ 58%, p = 0.0007). Urinary αCTX was increased (+ 31%, p = 0.03) whereas urinary (− 15%, p = 0.022) and serum (− 9.9%, p = 0.0056) βCTX were significantly decreased, resulting in a 49% ( p < 0.001) higher urinary α/βCTX ratio. Patients with Col I gene mutations resulting in haploinsufficiency had lower PINP levels than patients with helical domain alterations (26.4 ± 15.3 vs 41.6 ± 27.4 ng/ml, p = 0.0043) and controls ( p < 0.01). Conclusion Adults with OI are characterized by decreased Col I synthesis – especially those with haploinsufficiency mutations – increased Col I degradation and decreased Col I C-telopeptide isomerization.

Clinical update of pulsed electromagnetic fields on osteoporosis

To understand the effects of low-frequency pulsed electromagnetic fields (PEMFs) on chronic bony pain, bone mineral density (BMD), bone strength and biochemical markers of bone metabolism in the patients of osteoporosis. Using the key words "pulsed electromagnetic fields" and "osteoporosis", we searched the PubMed for related studies published in English from January 1996 to December 2007. We also searched the China National Knowledge Infrastructure (CNKI) for studies published in Chinese from January 1996 to December 2007. (1) all articles which referred to the effects of low-frequency pulsed magnetic fields on osteoporosis either in primary osteoporosis or secondary osteoporosis; (2) either observational studies or randomized controlled studies. (1) articles on experimental studies about osteoporosis; (2) repetitive studies; (3) case reports; (4) meta analysis. Totally 111 related articles were collected, 101 of them were published in Chinese, 10 were in English. Thirty-four were included and the remaining 84 were excluded. Low-frequency PEMFs relieves the pain of primary osteoporosis quickly and efficiently, enhances bone formation and increases BMD of secondary osteoporosis. But the effects of PEMFs on bone mineral density of primary osteoporosis and bone resorption were controversial.

MINERAL'NAYa PLOTNOST' KOSTII POKAZATELI KOSTNOGO METABOLIZMAU PATsIENTOV S IDIOPATIChESKIM VARIANTOM TsENTRAL'NOGO NESAKhARNOGO DIABETA (TsND)

Central diabetes insipidus is a rare pituitary disease due to impairment of synthesis or/and secretion of vasopressin (AVP), characterized by polyuria, polydipsia, low urine osmolality and hyperosmolality of plasma. Main therapy for CDI is substitutive therapy with desmopressin. Lately, it has been shown that AVP stimulates bone formation through the induction of PG synthesis in mesangial cells, contributing to prevent osteoporosis. Pivonello et al. (1998) found that patients with CDI even on nasal desmopessin therapy had a significant impairment in BMD and serum osteocalcin. The aim of this study was to assess the biochemical parameters of bone metabolism and the bone mineral density (BMD) in patients with idiopathic variant of CDI, treated with oral desmopressin. In 24 patients with idiopathic CDI, treated with oral desmopressin and 24 healthy controls we evaluated BMD (analyzer Prodigy, Lunar, DXA), serum osteocalcin (OK) and C-terminal telopeptide of type I collagen (CTx), (ECLIA, Roche Elecsys 1010/2010) as well as calcium total, ionized calcium and alkaline phosphatase (analyzer Hitachi 912, commercial kits Roche). Anterior pituitary dysfunction and concomitant conditions associated with osteoporosis were eliminated on clinical and laboratory basis. The results showed no significant differences between study groups with the exception for ionized calcium which was higher in the group of CDI (p=0,02). We were not able to confirm detrimental effects of idiopathic CDI on BMD and biochemical markers of bone metabolism.

Mineral Status of COPD Patients under Long‐Term Inhaled Corticosteroid Therapy

The aim of this study was to determine the mineral status of mandibles, femurs, and spines in chronic obstructive pulmonary disease (COPD) patients under long-term inhaled corticosteroid therapy. Pulmonary function tests were conducted on patients (n = 30) with COPD under inhaled corticosteroid therapy for at least 1 year. The results were compared to sex- and age-matched controls (n = 30). Analyses of blood gases were also carried out relative to COPD, and bone mineral densities (BMD) of the mandible, lumbar spine, femoral neck, trochanter, and Ward's triangle were also measured by dual-energy X-ray absorptiometry (DEXA). Levels of serum osteocalcin, alkaline phosphatase, calcium, phosphorus, and cortisol were also assessed. In accordance with the Global Initiative for Chronic Obstructive Lung Disease criteria, 8 of the COPD patients had moderate, 11 patients had severe, and 11 patients had very severe forms of the disease. All BMD measurements were lower in the COPD patients than in the control group. The serum osteocalcin levels in COPD patients were significantly lower than those in the control group (p < 0.0001). Serum calcium (p < 0.004) and cortisol levels (p < 0.026) in the COPD patients were also significantly lower than those in the control subjects. Although serum alkaline phosphatase level was higher and the phosphorus level was lower in the treatment group than in the control group, the differences were not statistically significant. Regular evaluation of the biochemical markers of bone metabolism and BMD would be helpful for detecting any detrimental changes of bone in COPD patients under long-term inhaled corticosteroid therapy. In this study, mandibular BMD was observed to be lower in COPD patients under long-term inhaled corticosteroid therapy than in healthy subjects. Thus, dental implant treatment may require preventive measures in COPD patients under long-term inhaled corticosteroid therapy.

Short-term effects of glucocorticoid therapy on biochemical markers of bone metabolism in Japanese patients: a prospective study

Glucocorticoid (GC) therapy induces rapid bone loss, but the early changes in calcium and bone metabolism in patients treated with GC have not been clarified. To investigate the changes in calcium and bone metabolism during the early stage of GC therapy, we analyzed various biochemical markers of bone metabolism. The serum levels of calcium (Ca), phosphorus, parathyroid hormone (PTH), osteocalcin (OC), bone alkaline phosphatase (BAP), and type I collagen cross-linked N-telopeptide (NTx), as well as the urinary levels of Ca, creatinine, and NTx, were measured on days 0, 3, 7, and 28 of GC therapy. The subjects were divided into the following four groups: 9 patients receiving pulse therapy (P), 18 patients receiving prednisolone (PSL) at doses > or =40 mg/day (H), 9 patients receiving PSL at doses > or =20 mg/day (M), and 11 patients receiving PSL at doses < or =10 mg/day (S). The serum OC level showed a marked decrease on day 3 of GC therapy (-41.2% +/- 6.6%, P < 0.01), while the BAP level decreased gradually. Both serum and urinary NTx levels significantly increased on day 7 of GC therapy (9.9% +/- 4.5%, P < 0.05, and 42.2% +/- 10.6%, P < 0.01, respectively). Urinary Ca excretion was increased on day 3 of GC therapy and continued to increase until 4 weeks, while intact PTH showed an increase on day 3 and then remained constant until 4 weeks. In groups P and H, there were significant early changes in OC, BAP, NTx, and intact PTH levels, as well as urinary Ca excretion. Even a PSL dose of <10 mg/day caused a decrease in the serum OC level. In conclusion, the biochemical markers of Ca and bone metabolism showed different kinetics depending on the dose of GC, and it is important for patients on high-dose GC therapy to receive prophylaxis for bone loss from the start of GC treatment.

Use of new biochemical markers in diagnosis of aseptic hip endoprosthesis loosening

Aseptic loosening of endoprosthesis is the most important problem in total hip arthroplasty. The diagnosis of aseptic loosening is based on anamnesis, the clinical findings, the radiography and scintigraphy. Despite the multitude of diagnostic possibilities it is still a problem to get an exact and early diagnosis. The process of loosening in the bone interface always leads to a change of bone structure of the surrounding bone tissue. In a prospective study we measured biochemical markers of bone metabolism in serum and urine to evaluate a possible change occurring parallel to endoprotheic loosening. 37 patients with severe signs of loosening (later intraoperatively confirmed) and 30 patients without any clinical or radiological signs of loosening (control group) were induced. Gender, age and model of endoprosthesis were similar in both groups. Parameters of bone formation (osteocalcin, alkaline phosphatase, procollagen I C-terminal extension peptide) and bone resorption (Cross-linked n-terminal telopetide) were measured. The cross-linked n-terminal telopetide (NTX) was significant increased in the loosening group (p < 0.001). Of the measured bone formation markers only osteocalcin showed a significantly higher level in patients with endoprosthetic loosening (p < 0.002). All other measured parameters of the bone metabolism showed no significant differences between the both groups. Our results show, that biochemical markers can provide relevant information of endoprosthesic loosening. We are now analysing in a prospective longitudinal study whether these parameters are also suitable to detect early endoprosthetic loosening.

Effects of tibolone and raloxifene on bone mineral density in osteopenic postmenopausal women

A randomized trial was conducted in osteopenic postmenopausal women to compare the efficacy of tibolone versus raloxifene on BMD of the lumbar spine and hip. Tibolone increased lumbar spine and total hip BMD to a statistically significantly greater extent than raloxifene after two years of treatment. Both tibolone, a selective tissue estrogenic activity regulator (STEAR), and raloxifene, a selective estrogen receptor modulator (SERM), are known to prevent postmenopausal bone loss. However, no head-to-head studies to compare the efficacy on bone have been performed. A double-blind, randomized trial was conducted in osteopenic postmenopausal women aged 60-79 years to compare the effects of tibolone 1.25 mg/day to raloxifene 60 mg/day on bone mineral density (BMD). Serum osteocalcin and serum type I collagen C-telopeptides were measured as biochemical markers of bone metabolism. Three hundred and eight subjects were allocated to treatment. Both treatments significantly increased lumbar spine BMD, however the increase was significantly larger after tibolone treatment than after raloxifene treatment (at year 1: 2.2% versus 1.2%, p<0.01 and at year 2: 3.8% versus 2.1%, p<0.001). After 2 years of treatment, the increase in total hip BMD in the tibolone group was significantly larger than in the raloxifene group (p<0.05). Both treatments significantly reduced type I collagen C-telopeptides and osteocalcin levels when compared to baseline. Tibolone 1.25 mg/day for 2 years prevents postmenopausal bone loss in older women and results in a larger increase of BMD both at the lumbar spine and hip than raloxifene.

Response of biochemical markers of bone metabolism to exercise intensity in thoroughbred horses.

We studied the response of biochemical markers of bone metabolism to exercise intensity in horses. Four horses were walked on a mechanical walker for one week (pre-exercise). Then they performed low-speed exercise on a high-speed treadmill in the first week and medium-speed exercise in the second week and high-speed exercise in the third week of training. We measured two indices of bone resorption, serum hydroxyproline concentration and the urinary deoxypyridinoline/creatinine ratio, and serum osteocalcin (OC) concentration as an index of bone formation. Both indices of bone resorption gradually decreased during the experiment. Serum OC concentration did not change in the first week but was significantly lower in the second and the third weeks compared to in the pre-exercise period and in the first week. These results suggest that the low-speed exercise decreased bone resorption but did not affect bone formation, which possibly results in increasing bone mineral content and strengthening of bones. The high-speed exercise decreased bone formation and bone resorption, i.e., bone turnover was suppressed. The low-speed exercise may be preferable for increasing bone mineral content.

Altered Bone Metabolic Markers In Type 2 Diabetes Mellitus: Impact of Glycemic Control

To study the influence of glycemic control on bone minerals and biochemical markers of bone metabolism in patients with type 2 diabetes mellitus. A Case-control study was conducted at Uhod Hospital, KSA from October 2003 to August 2004 to study 60 premenopausal, multipareous female patients with type 2 diabetes mellitus for >5 years, under oral anti-diabetics, with no diabetic complications. They were divided according to their glycemic control into: controlled group (n=22) and poorly controlled group (n=38) and were compared to 30 age matched healthy women. Osteocalcin (OC), urinary deoxypyridinoline (Dpd), Parathyroid hormone (PTH) were measured by chemiluminescent enzyme immunometric assay and 25 hydroxy vitamin D (25 OH-D) was measured by high performance liquid chromatography. In both diabetic groups, there were higher ALP (177± 39.88 & 287 ± 41.4 mg/dl) and PTH (49 ±9.87 & 56.25± 12.3 Pg/ml) than in controls (144 ± 22.54 mg/dl, 26.9± 5.60 Pg/ml respectively), but lower serum calcium (8.87± 0.3 & 8.79 ±0.7 mg/dl), and 25 OH-D (50.9±12.6, 45.4±18.9 μg/l) and osteocalcin (4.09 ± 1.48 & 1.89 ± 0.24 ng/ml) than controls (9.96± 1.9l, 57.9±13.6 μg/l, 6.5±1.5 ng/ml respectively), Urinary calcium and urinary Dpd were higher (270.66±41.7 & 300.56 ± 55.67 mg/d & 10.8 ± 4.6, 12.06±5.12 nM/mM creatinine) than in controls (244.23 ±51.5 mg/d, 6.2 ±0.8 nM/mM creatinine). Glycemic indices (FBG, HbA1C) showed significant positive correlation with ALP (r=0.290 & 0.294), urinary calcium (r=0.340 & 0.260) and Dpd (r=0.468 & 0.228). Our data give evidence of altered bone metabolic markers in both controlled and uncontrolled female patients with type 2 diabetes mellitus with more significant alterations in the uncontrolled group. This could reflect the strong impact of glycemic control on diabetic bone turnover.

.BETA.-Cryptoxanthin and Bone Metabolism: The Preventive Role in Osteoporosis

Bone loss with aging induces osteoporosis. The most dramatic expression of the disease is represented by fractures of the proximal femur. Pharmacologic and nutritional factors may play a role in the prevention of bone loss with aging. β-Cryptoxanthin, a kind of carotenoid, is abundant in Satsuma mandarin orange (Citrus unshiu MARC.). Amoung various carotenoids including β-cryptoxanthin, lutein, lycopene, β-carotene, astaxanthin, and rutin, β-cryptoxanthin has been found to have a unique anabolic effect on bone calcification in vitro. Hesperidin, which is contained in Satsuma mandarin orange, did not have an anabolic effect on bone calcification in vitro. β-Cryptoxanthin has stimulatory effects on osteoblastic bone formation and inhibitory effects on osteoclastic bone resorption in vitro, thereby increasing bone mass. β-Cryptoxanthin has an effect on the gene expression of various proteins which are related to osteoblastic bone formation andmineralization in vitro. β-Cryptoxanthin has inhibitory effects on enzyme activity which is related to osteoclastic bone resororption, and the carotenoid induces apoptosis of mature osteoclastic cells in vitro. Oral administration of β-cryptoxanthin has been shown to have the anabolic effects on bone components in young and aged rats, and the administration has the preventive effects on bone loss in streptozotocin-diabetic rats and ovariectomized rats in vivo. Moreover, the intake of β-cryptoxanthin-reinforced juice for longer periods has been shown to have both stimulatory effects on bone formation and inhibitory effects on bone resorption in healthy human or postmenopausal women in evaluating with serum biochemical markers of bone metabolism in vivo. Thus the intake of dietary β-cryptoxanthin may have a preventive effect on osteoporosis due to stimulating bone formation and due to inhibiting bone resorption. Moreover, epidemiological studies suggest the potential role of β-cryptoxanthin as a sustainable nutritional approach to improving bone health of human subjects. β-Cryptoxanthin is an important food factor in maintaining bone healthy and in preventing osteoporosis.

Treatment of symptomatic uterine leiomyoma with letrozole

Uterine leiomyomas are the most common benign tumours of the female genital tract, often necessitating hysterectomy. The most common symptoms are dysmenorrhoea, menorrhagia, infertility and abortion. Ovarian hormones seem to play an essential role in pathogenesis, and deprivation of ovarian oestrogen causes leiomyomas to shrink significantly. The purpose of this study was to evaluate the effects of the non-steroidal aromatase inhibitor letrozole on uterine leiomyomas and on bone metabolism. A prospective, open clinical trial was conducted in a university-based hospital. Sixteen premenopausal women with symptomatic uterine leiomyomas were treated with letrozole 5 mg/day orally for 3 months. The main outcome measures of uterine and uterine leiomyoma sizes, serum FSH, LH, oestradiol concentrations, ovarian volumes and myoma-related symptoms were noted at baselines and once a month during treatment. Lumbar spine bone mineral density and biochemical markers of bone metabolism were studied at the beginning and at the end of 3 months. Letrozole significantly decreased uterine leiomyoma sizes ( P < 0.01) and promptly benefited women with heavy menstrual bleeding associated with leiomyomas without changing bone mineral density. Aromatase inhibitors may represent a new generation of medications for the treatment of leiomyoma and associated symptoms. Larger clinical trials are needed, however, to fully evaluate their safety and efficacy.

Cyclic Pamidronate Therapy in Children with Osteogenesis Imperfecta: Results of Treatment and Follow-up After Discontinuation

Cyclic intravenous pamidronate treatment is widely used for symptomatic therapy of osteogenesis imperfecta (OI). However, data after discontinuation are very limited. The results of cyclical pamidronate treatment in 14 patients with moderate/severe OI and follow up of six of them after discontinuation are presented to assess the effects of pamidronate and its discontinuation. Pamidronate was administered at a dosage of 0.5 mg/kg for 3 successive days every 2 months in 14 patients with OI aged 5.10 +/- 3.68 years. Treatment was stopped in six patients after a duration of 16.33 +/- 4.63 months, due to stable bone mineral density (BMD) values and/or no fracture in the last 6 months, or due to family demand. The main outcome measures were areal BMD (aBMD) of the lumbar spine, biochemical markers of bone metabolism, fracture rate, and clinical evaluation. Areal BMD and aBMD z-scores showed significant improvement during the treatment period. Both serum and bone-specific alkaline phosphatase values were significantly decreased. Fracture rate reduced significantly from 3.5 +/- 1.01 to 0.83 +/- 0.77 fractures/year. Bone pain, which was severe in five patients, disappeared just after the first cycle, and the activity and mobility of patients increased. aBMD and aBMD z-scores were decreased 1.5 years after discontinuation, although not statistically significant. Annual fracture rate increased significantly. Bone pain recurred in four patients. Pamidronate treatment was reinstituted in five of these patients at the end of 1.5 years. Cyclical pamidronate treatment is very effective in children with moderate/severe OI. This treatment should be started early enough before the occurrence of irreversible deformities and must be given for a longer time during the growth period.

High serum YKL‐40 concentration is associated with severe bone disease in newly diagnosed multiple myeloma patients

In multiple myeloma (MM) YKL-40 is present in the bone marrow microenvironment and is suggested to play a role in remodelling of the extracellular matrix. Here, the association between serum YKL-40 and severity of bone disease in MM is investigated. Serum YKL-40 was measured in 34 MM patients at diagnosis. Bone disease was assessed by radiography and biochemical markers of bone metabolism. Patients were treated with conventional chemotherapy and followed for up to 30 months. Patients with a serum YKL-40 elevated above the age specific reference range (56%) had a higher total X-ray score (P = 0.003) and higher levels of the markers of bone resorption serum C-terminal telopeptide of collagen type I (P = 0.003), urine pyridinoline (P = 0.04) and urine deoxypyridinoline (P = 0.002), while the levels of urine N-terminal telopeptide of collagen type I (NTX-1) and the markers of bone formation equalled those seen in patients with a normal serum YKL-40. Serum YKL-40 level (beta = 7.6; P = 0.002) and urine NTX-1 (log(2)) (beta = 3.5; P = 0.006) were independent predictors of total X-ray score at diagnosis. Patients with elevated serum YKL-40 at diagnosis had shorter time to first osteolytic event compared to patients with normal serum YKL-40 (12 months vs. not reached; Log rank test: P = 0.03). Newly diagnosed MM patients with elevated serum concentrations of YKL-40 have more severe bone destruction including increased bone resorptive activity and shorter time to progression of bone disease. At this point, a potential role for YKL-40 in myeloma-related bone disease must be considered.

Specific Effects of γ-Linolenic, Eicosapentaenoic, and Docosahexaenoic Ethyl Esters on Bone Post-ovariectomy in Rats

Long chain polyunsaturated fatty acids (LCPUFAs) are involved in the regulation of bone metabolism. Increased dietary consumption of n-3, and possibly some n-6, LCPUFAs may limit postmenopausal bone loss. The aim of this study was to determine the effects on bone of specific fatty acids within the n-3 and n-6 LCPUFA families in ovariectomized (OVX) rats. Rats were OVX or sham-operated and fed either a control diet (OVX and sham) or a diet supplemented with 0.5 g/kg body weight/day of gamma-linolenic (GLA), eicosapentaenoic (EPA), docosahexaenoic (DHA) ethyl esters or a mixture of all three (MIX) for 16 weeks. Bone mineral content (BMC), area, and density and plasma concentrations of insulin-like growth factor-I, vitamin D, selected biochemical markers of bone metabolism, and parathyroid hormone (PTH) were determined. The OVX-induced decrease in lumbar spine BMC was significantly attenuated by DHA but not by EPA or GLA supplementation or supplementation with a mixture of all three LCPUFAs. Endosteal circumferences of tibiae were significantly greater in DHA and EPA compared to OVX. Plasma C-terminal telopeptide of type I collagen and osteocalcin concentrations were not significantly different in the DHA group compared to OVX. Femur BMC decreased by a significantly greater amount in GLA than OVX, and final plasma PTH concentrations were significantly higher in GLA compared to all other groups. In conclusion, DHA ameliorated OVX-induced bone mineral loss. GLA exacerbated post-OVX bone mineral loss, possibly as a result of PTH-induced bone catabolism.

Evaluation of Serum Osteocalcin and CTX‐I in Ardenner Horses with Special Reference to Juvenile Interphalangeal Joint Disease

The first aim of this study was to establish a profile of age-related normal serum concentrations of osteocalcin (OC) in Ardenner horses. For this first part, blood samples from 49 healthy Ardenner horses were collected. The second aim was to study two biochemical markers of bone metabolism, OC and a carboxy-terminal cross-linking telopeptide of type I collagen (CTX-I), in 30 young Ardenner horses during 1 year. Amongst them, 17 showed lesions of juvenile degenerative joint disease in the distal forelimbs. A specific radioimmunoassay for equine OC was used to measure the serum concentration of the marker. The serum concentration of CTX-I was measured using a commercially available human assay validated for use in the horse. The effect of age, sex, season and health status (with or without lesions) was assessed. Levels of OC fall between birth and the adult stage: this decrease being most marked between birth and 1 year of age. This age-related decrease of OC was confirmed in the 30 young Ardenner horses, but CTX-I levels remained constant in this group. The Levels of the two markers changed significantly with the season with higher concentrations during the winter. No significant difference was shown either between the two sexes or between the two health statuses.

Evaluation of 41Calcium as a New Approach to Assess Changes in Bone Metabolism: Effect of a Bisphosphonate Intervention in Postmenopausal Women With Low Bone Mass

A new technique was evaluated to identify changes in bone metabolism directly at high sensitivity through isotopic labeling of bone Ca. Six women with low BMD were labeled with 41Ca up to 700 days and treated for 6 mo with risedronate. Effect of treatment on bone could be identified using 41Ca after 4-8 wk in each individual. Isotopic labeling of bone using 41Ca, a long-living radiotracer, has been proposed as an alternative approach for measuring changes in bone metabolism to overcome current limitations of available techniques. After isotopic labeling of bone, changes in urinary 41Ca excretion reflect changes in bone Ca balance. The aim of this study was to validate this new technique against established measures. Changes in bone Ca balance were induced by giving a bisphosphonate. Six postmenopausal women with diagnosed osteopenia/osteoporosis received a single oral dose of 100 nCi 41Ca for skeleton labeling. Urinary 41Ca/40Ca isotope ratios were monitored by accelerator mass spectrometry up to 700 days after the labeling process. Subjects received 35 mg risedronate per week for 6 mo. Effect of treatment was monitored using the 41Ca signal in urine and parallel measurements of BMD by DXA and biochemical markers of bone metabolism in urine and blood. Positive response to treatment was confirmed by BMD measurements, which increased for spine by +3.0% (p = 0.01) but not for hip. Bone formation markers decreased by -36% for bone alkaline phosphatase (BALP; p = 0.002) and -59% for procollagen type I propeptides (PINP; p = 0.001). Urinary deoxypyridinoline (DPD) and pyridinoline (PYD) were reduced by -21% (p = 0.019) and -23% (p = 0.009), respectively, whereas serum and urinary carboxy-terminal teleopeptides (CTXs) were reduced by -60% (p = 0.001) and -57.0% (p = 0.001), respectively. Changes in urinary 41Ca excretion paralleled findings for conventional techniques. The urinary 41Ca/40Ca isotope ratio was shifted by -47 +/- 10% by the intervention. Population pharmacokinetic analysis (NONMEM) of the 41Ca data using a linear three-compartment model showed that bisphosphonate treatment reduced Ca transfer rates between the slowly exchanging compartment (bone) and the intermediate fast exchanging compartment by 56% (95% CI: 45-58%). Isotopic labeling of bone using 41Ca can facilitate human trials in bone research by shortening of intervention periods, lowering subject numbers, and having easier conduct of cross-over studies compared with conventional techniques.

The Use of Bone Markers in a 6-Week Study to Assess the Efficacy of Oral Clodronate in Patients with Metastatic Bone Disease

Biochemical markers of bone metabolism are strongly associated with skeletal complications in metastatic bone disease. The bisphosphonate clodronate reduces skeletal morbidity by inhibiting bone resorption. This study investigated the use of bone markers to assess the efficacy of oral clodronate across a range of clinically relevant doses. There were 125 patients with metastatic bone disease randomized to daily oral clodronate (800, 1,600, 2,400 and 3,200 mg) or placebo in a double-blind, multicenter study. Urinary N-terminal telopeptide of type I collagen (U-NTX), serum C-terminal telopeptide of type I collagen (S-CTX), urinary calcium (U-Ca), and bone alkaline phosphatase were measured weekly for a 6-week treatment period. Doses of >or=1,600 mg clodronate produced mean reductions of >40% in U-NTX, S-CTX and U-Ca, all significantly different from placebo (P=0.0015, 0.001, 0.0036, respectively), after 6 weeks. Evaluation of least significant changes in markers suggested that the commonly used 1,600 mg dose was most appropriate for breast cancer patients. However, this dose was suboptimal for other (mainly prostate cancer) patients, who showed better response to 2,400 mg. The number of adverse events in the treatment arms was not significantly different from that in placebo, but a higher number of patients had diarrhea in the 3,200 mg arm and withdrew from the study. This trial is the first to explore the dose-response relationship of clodronate in oncology using specific markers of bone turnover. It has confirmed that the 1,600 mg dose is safe and effective for breast cancer patients but may be suboptimal for the other tumors studied.

Hospital based preliminary study on osteoporosis in postmenopausal women

The awareness of osteoporosis has grown world wide in recent years. This silently progressing metabolic bone disease is widely prevalent in India, and osteoporotic fractures are a common cause of morbidity and mortality in adult Indian men and women. Rapid bone loss occurs in postmenopausal women due to hormonal factors which lead to increased risk of fractures. Biochemical markers of bone metabolism are used to assess skeletal turnover. A cross-sectional study of 150 pre- and post menopausal women was carried out at S.D.M College of Medical Sciences and Hospital, Dharwad, during the period of May 2005 to September 2005. The study group consisted of 75 Premenopausal women in the age group of 25-45 years and 75 Postmenopausal women in the age group of 46-65 years. Bone formation markers (Total Calcium, lonised calcium, Phosphorus, Alkaline phosphatase), and bone resorption markers (Urinary Hydroxyproline) were analysed in pre and post menopausal women. Bone formation markers, Total and lonised calcium were significantly decreased (p<0.001) and Alkaline phosphatase was significantly increased (p<0.001) in postmenopausal women compared to premenopausal women. Bone resorption markers, Urinary hydroxyproline excretion was significantly increased (p<0.001) in postmenopausal women. The results from this study suggest that simple, easy, common biochemical markers can still be used to assess the bone turnover in postmenopausal women and hence their risk of developing osteoporosis and fractures.

Effects of parathyroidectomy on bone remodeling markers and vitamin D status in patients with chronic kidney disease–mineral and bone disorder

Chronic renal failure (CRF) is often associated with bone disorders including chronic kidney disease-mineral and bone disorder (CKD-MBD). Parathyroid hormone (PTH) has a relationship to bone remodeling, and so this study was undertaken to evaluate changes in bone remodeling markers after parathyroidectomy (PTX). Twelve adult patients, mean age 43.4 +/- 12.7 years, of both genders, were evaluated, prior to and six months after PTX. Analysis of biochemical markers of bone metabolism, such as total and ionized calcium, phosphorus, 25(OH)D(3), total alkaline phosphatase (TAP), bone-specific alkaline phosphatase (BAP), intact PTH, osteoprotegerin (OPG), and tartrate-resistant acid phosphatase isoform 5b (TRAP), were measured. No changes were observed after PTX in the serum total and ionized calcium, TAP, BAP, and 25(OH)D(3). After surgery there was a significant decrease in serum phosphorus, iPTH, and TRAP (P < 0.001). No significant change was observed in OPG; however there was a positive correlation between OPG and 25(OH)D(3) before and after surgery (r = 0.774, P = 0.014; and r = 0.706, P = 0.01, respectively). The percentage of patients with vitamin D deficiency decreased from 16.7% to 8.3%, while those with sufficient levels increased from 41.7% to 58.3%. The small number of patients in the study notwithstanding, the present study is unique because it provides information on bone metabolism and vitamin D status six months after PTX. The removal of parathyroid glands significantly decreased bone resorption and indicated a tendency of 25(OH)D(3) concentration to increase. However, the precise role of OPG and BAP in the improvement in bone remodeling in patients with CKD-MBD requires further study.