Levels Of Bone Metabolic Markers Research Articles

Clinical results of alendronate monotherapy and combined therapy with menatetrenone (VitK2) in postmenopausal RA patients

We aimed to evaluate the clinical efficacy of monotherapy with alendronate and combined therapy with alendronate and menatetrenone (vitamin K2 [VitK2]) in postmenopausal rheumatoid arthritis (RA) patients with osteoporosis or osteopenia. Sixty-two postmenopausal RA patients with untreated osteoporosis or osteopenia (lumbar spine bone density ≤80 % of young adult mean [YAM]) were enrolled: 39 had abnormal serum undercarboxylated osteocalcin (ucOC) levels (>4.5 ng/mL) and received combined therapy with alendronate (35 mg/week) and VitK2 (45 mg/day) (ALN + K group); 23 had normal ucOC levels (≤4.5 ng/mL) and received alendronate monotherapy (35 mg/week) (ALN group). The clinical results for the 57 patients in both groups were evaluated after 1-year treatment. The mean baseline/follow-up (FU) lumbar spine bone density (%YAM) values were 73.0/76.8 % (P < 0.01) in the ALN + K group and 77.0/80.3 % (P < 0.01) in the ALN group; a significant increase was shown in both groups. Mean proximal femoral bone density values at baseline/FU were 71.4/73.8 (P < 0.01) in the ALN + K group and 71.4/71.6 % (not significant; NS) in the ALN group; a significant increase was shown in the ALN + K group only. Serum ucOC levels were normalized in the ALN + K group at FU. At FU, bone metabolism markers [bone-specific alkaline phosphatase (BAP) and N-terminal cross-linked telopeptides of type I collagen] were decreased in both groups. One patient in the ALN + K group and three in the ALN group suffered new fractures. Combined therapy with alendronate and VitK2 decreases bone metabolism marker levels and serum ucOC levels, and increases lumbar spine and femoral neck bone density in postmenopausal RA patients with abnormal ucOC levels and osteoporosis or osteopenia.

Factors predicting bone mineral density (BMD) changes in young women over a one-year study:changes in body weight and bone metabolic markers during the menstrual cycle and their effects on BMD.

Currently, 26% of Japanese women in their twenties are under weight, and therefore at risk of developing various metabolic abnormalities due to an inadequate nutrient intake, which in turn affects the acquisition of a peak bone mineral density (BMD). In this study, we aimed to clarify the effects of menstrual cycle-related changes in body weight and bone metabolic marker levels on the BMD changes. The subjects were 42 women (19.6 ± 0.8 years). The levels of osteocalcin (OC), BAP, s-NTx, u-DPD, and E2 in the menstrual and ovulatory phases were measured. The associations between dependent variables (BMD changes/year in the lumbar spine, femur, femoral neck) and explanatory variables (body weight changes/year, the levels of OC, BAP, s-NTx, u-DPD) were evaluated using multiple regression analysis. Analysis of the correlations between the changes in bone metabolic markers and changes in BMD showed a correlation between the OC level in the menstrual phase and changes in the BMD of the entire femur, suggesting that a high OC level protects against BMD reduction, probably by promoting osteoblast activity, and that bone formation activity suppresses the decrease in BMD. These results suggest that, to predict BMD changes from bone metabolic markers in young women, it is necessary to measure OC levels in the menstrual phase.

Association of the A1330V and V667M polymorphisms of LRP5 with bone mineral density in Greek peri- and postmenopausal women

Wnt signaling through low-density lipoprotein receptor-related protein 5 (LRP5) is an important determinant of bone mass regulation. Objective To explore the influence of two LRP5 single nucleotide polymorphisms (SNPs) A1330V and V667M on bone mineral density (BMD) and serum levels of osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL) and bone metabolic markers in a Greek female population. Study design Two hundred and nine postmenopausal and twelve perimenopausal women aged 40–63 years were enrolled. All participants underwent spinal BMD evaluation. Genotyping of A1330V and V667M polymorphisms was performed by real-time polymerase chain reaction. Levels of OPG, soluble RANKL (sRANKL) and bone metabolic markers were measured. Results As regards A1330V SNP, women carrying CT/TT genotypes had lower spinal BMD than women with CC ( p < 0.0001). Regarding V667M SNP, spinal BMD was lower in women with GA/AA than in women with GG genotypes ( p < 0.0001). These differences remained significant after adjustment for age, years since menopause and body mass index. The A1330V and V667M polymorphisms were in strong linkage disequilibrium. A significant interaction between A1330V and V667M SNPs on spinal BMD was revealed. The haplotype with both risk alleles of the two SNPs (AT) conferred more risk for low BMD than the haplotypes with one risk allele (GT or AC) or the haplotype-reference (GC) ( p = 0.046, p = 0.045, and p = 0.010, respectively). No effect was observed on circulating OPG, sRANKL levels and bone metabolic markers. Conclusions These findings demonstrate that the A1330V and V667M polymorphisms are associated with low BMD in peri- and postmenopausal Greek women.

The ESR2 AluI gene polymorphism is associated with bone mineral density in postmenopausal women

Multiple factors may contribute to the pathogenesis of postmenopausal osteoporosis including environmental, life-style and genetic factors. Common variants in ESR2 gene encoding for ER-beta, highly expressed in bone tissue, have recently been proposed as candidates for affecting bone phenotype at the population level, particularly in postmenopausal women. In this study, we examined the genetic background at ESR2 AluI (rs4986938, 1730G>A) locus in 89 osteopenic, postmenopausal women (age range 49–56 years) together with BMD at lumbar spine and femoral neck sites as well as variations in plasma levels of bone metabolism and turnover markers. Genotyping for ESR2 G1730A polymorphism showed that the frequency of A mutated allele accounted for 0.4 in our cohort of postmenopausal women; moreover, the GA1730 heterozygous individuals were the most represented (50.6%) compared with GG (37.8%) and AA homozygous ones (14.6%). A regression analysis showed that lumbar spine BMD values were significantly associated with both ESR2 AA1730 genotype ( p = 0.044) and time since the onset of menopause ( p = 0.031), while no significant association was detected between biochemical markers and genetic background. Interestingly, 85% of patients with AA1730 genotype presented the smallest lumbar spine BMD values. These findings first indicate a worsening effect of ESR2 AluI polymorphism on lumbar spine BMD reduction in postmenopause, suggesting that the detection of this ESR2 variant should be recommended in postmenopausal women, particularly in populations with a high prevalence of ESR2 AA1730 homozygous genotype.

Bone Metabolism Markers in Sportswomen with Menstrual Cycle Dysfunctions

Bone Metabolism Markers in Sportswomen with Menstrual Cycle DysfunctionsIt is a well known fact that sportswomen with irregular menstrual cycle are exposed to the risk of diminished bone mineral density, and consequentially osteoporosis may appear. Monitoring of the levels of biochemical markers of bone metabolism enables understanding of the dynamic changes during the bone remodeling process. The objectives of the conducted research were to determine the prevalence of menstrual dysfunctions in a sports-women sample and a control group, and also to determine the levels of bone metabolism markers in groups of women with menstrual dysfunctions. The women (n=117) were separated into two groups, the experimental group (S) (n=84) comprised of three subgroups of sports women (34 women who play ball game sports, 27 athletes and 23 sport dancers) and the control group (C) (n=34). To establish the menstrual profile and dysfunction of the menstrual cycle, we used a very detailed questionnaire. The level of mid-fragment osteocalcin (N-MID osteocalcin) as a marker of bone formation was deter mined, as well as β-Cross Laps (β-CTx-bone resorption marker) via the electro luminescent immunochemistry method on an Elecsys 1010 automated machine. Primary amenorrhea was found in 7 (8.33%) and oligomenorrhea in 11 (13.09%) sportswomen, which was statistically a much higher incidence (p&lt;0.05) than in the control group (0/34). Values of bone metabolism markers showed a statistically significant difference in the level of the bone resorption marker β-CrossLaps between the groups of amenorrheic and oligomenorrheic sportswomen in comparison to the eumenorrheic women, both sportswomen and those in the control group. Accelerated resorption was accompanied with accelerated bone formation. Menstrual dysfunctions were statistically more present in the sports-women group than in the control group and were accompanied with accelerated bone metabolism from the point of view of the increase of bone metabolism markers level.

Active Paget’s disease of bone with normal biomarkers of bone metabolism: a case report and review of the literature

Paget's disease of bone is a focal skeletal disorder characterized by the formation of structurally abnormal bone, skeletal deformities, and other complications leading to bone pain and significant disability. It can involve one or more areas in a single bone (monostotic) or multiple bones (polyostotic). Most of the time the disease is asymptomatic and the diagnosis is made incidentally by increased levels of bone metabolism markers, especially alkaline phosphatase and is confirmed by specific findings in radiographs and radionuclide bone scan. In this report, we describe the case of a 65-year-old female with clinical and radiological findings of active Paget's disease of bone, but with absence of abnormal biochemical markers. The patient was given a dose of 5mg zoledronic acid intravenously with significant clinical improvement within the next 6months. The present case not only shows that Paget's disease of bone can occur in the setting of normal markers of bone metabolism but also that, in such cases, the response to treatment can be monitored by improvement in the clinical picture or by correct evaluation of the imaging findings.

Serum concentrations of carboxylated osteocalcin are increased and associated with several components of the polycystic ovarian syndrome

Intriguing studies suggest that osteocalcin (OC) and its carboxylated (Gla)/uncarboxylated form are involved in the regulation of insulin secretion and action. Additionally, advanced glycated end products (AGEs) directly regulate the secretion of these osteoblast-derived molecules. In polycystic ovarian syndrome (PCOS), among the pathophysiological aberrations, deregulation of insulin secretion and action as well as elevated AGEs levels have been demonstrated. In this study, we evaluated the serum levels of osteocalcin and Gla osteocalcin and their possible associations with metabolic, hormonal, and ultrasonographic components of PSOS: 97 women were studied, 50 PCOS patients and 47 controls, matched for age and body mass index (BMI). In each subject, the levels of bone metabolism markers have been evaluated, and metabolic and hormonal profiles as well as ovarian ultrasound were carried out. Osteocalcin (4.30 ± 1.74 vs. 6.20 ± 1.78 ng/ml, P < 0.0005) values were significantly lower, whereas Gla osteocalcin (37.93 ± 6.87 vs. 9.64 ± 8.21 ng/ml, P < 0.0005) and receptor activator for nuclear factor-κB ligand (0.54 ± 0.26 vs. 0.16 ± 0.15 pmol/l, P < 0.0005) values were significantly higher in PCOS subjects compared to the control group, independently of obesity. A significant association was disclosed between osteocalcin and Gla osteocalcin with androgens, insulin resistance, AGEs, and ovarian morphology. Receiver operating curve analysis revealed that Gla osteocalcin [AUC, 0.975 (95% CI, 0.93-1.00)] as well as AGEs are significant prognostic factors of PCOS [AUC, 0.986 (95% CI, 0.97-1.00)]. Lower osteocalcin and elevated serum levels of its carboxylated form are displayed in PCOS subjects and are associated with several PCOS components. These findings suggest a potential interaction between bone-derived markers and the metabolic/hormonal abnormalities observed in PCOS. However, the pathophysiological mechanisms and moreover the possible clinical implications require further investigation.

859 RELATIONSHIP BETWEEN BONE MINERAL DENSITY AND ANDROGEN-DEPRIVATION THERAPY IN JAPANESE PROSTATE CANCER PATIENTS

You have accessJournal of UrologyProstate Cancer: Advanced III1 Apr 2010859 RELATIONSHIP BETWEEN BONE MINERAL DENSITY AND ANDROGEN-DEPRIVATION THERAPY IN JAPANESE PROSTATE CANCER PATIENTS Takeshi Yuasa, Shinya Maita, Norihiko Tsuchiya, Shunji Takahashi, Kiyohiko Hatake, Iwao Fukui, and Tomonori Habuchi Takeshi YuasaTakeshi Yuasa Tokyo, Japan More articles by this author , Shinya MaitaShinya Maita Akita, Japan More articles by this author , Norihiko TsuchiyaNorihiko Tsuchiya Akita, Japan More articles by this author , Shunji TakahashiShunji Takahashi Tokyo, Japan More articles by this author , Kiyohiko HatakeKiyohiko Hatake Tokyo, Japan More articles by this author , Iwao FukuiIwao Fukui Tokyo, Japan More articles by this author , and Tomonori HabuchiTomonori Habuchi Akita, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1615AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Androgen-deprivation therapy (ADT) of patients with prostate cancer (PCa) is known to reduce bone mineral density (BMD). However, most studies examined Caucasian or black patients and the effects of ADT on the bone metabolism of East Asians are unclear. Recently, racial differences between Caucasian and Japanese women were highlighted by a breast cancer study. Therefore, we performed a cross-sectional study to elucidate the influence of ADT on bone metabolism in Japanese patients. METHODS In total, 201 native Japanese patients with prostate cancer, of whom 113 were ADT-treated and 88 were hormone-naive, were enrolled. Lumbar spine, total hip, and femoral neck BMDs were measured by dual energy x-ray absorptiometry and expressed in standard deviation units relative to the scores of young adult men (T-score) or age-matched men (Z-score). Serum levels of bone metabolism markers were also measured. RESULTS The ADT-treated patients had significantly lower BMD values, T-scores, and even Z-scores than the hormone-naive patients (P<0.001). For patients who were hormone-naive, ADT-treated for less than 2 years, and ADT-treated for more than 2 years, the osteoporosis prevalence was 4.5% (4/88), 12.1% (4/33), and 10.8% (4/37), respectively (Figure). The patients who had high Gleason scores had significantly lower BMDs than those with lower Gleason scores (P<0.01). The ADT-treated patients had significantly higher serum NTx levels than the hormone-naive patients (P=0.014), but significantly lower serum ICTP levels than the ADT-treated patients with bone metastasis (P<0.001). CONCLUSIONS Our cross-sectional study demonstrated that both ADT-treated and hormone-naive Japanese prostate cancer patients have low rates of osteoporosis, which differs from observations of the BMDs of patients in western countries. Genetic and hormonal or other environmental factors may result in population differences in the characteristics of prostate cancer and BMD. To our knowledge, this is the first study to demonstrate the low prevalence of osteoporosis in both ADT-treated and hormone-naïve Japanese PCa patients. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e335 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Takeshi Yuasa Tokyo, Japan More articles by this author Shinya Maita Akita, Japan More articles by this author Norihiko Tsuchiya Akita, Japan More articles by this author Shunji Takahashi Tokyo, Japan More articles by this author Kiyohiko Hatake Tokyo, Japan More articles by this author Iwao Fukui Tokyo, Japan More articles by this author Tomonori Habuchi Akita, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Relationship Between Bone Mineral Density and Androgen-deprivation Therapy in Japanese Prostate Cancer Patients

To examine Japanese patients who had received androgen-deprivation therapy (ADT) for longer periods, as it is known that ADT of patients with prostate cancer reduces their bone mineral density (BMD). However, our previous cross-sectional study revealed that short-term ADT (average, 23.5 months) does not significantly increase the prevalence of osteoporosis in Japanese patients. The subjects consisted of 201 native Japanese patients with prostate cancer. They comprised 113 ADT-treated and 88 hormone-naive patients. Lumbar spine, total hip, and femoral neck BMDs were measured by dual-energy x-ray absorptiometry and expressed in standard deviation units relative to the scores of young adult men (T-score) or age-matched men (Z-score). Serum levels of bone metabolism markers were also measured. The ADT-treated patients had significantly lower BMD values, T-scores, and even Z-scores than the hormone-naive patients (P <.001). For patients who were hormone-naive, ADT-treated for less than 2 years, and ADT-treated for more than 2 years, the osteoporosis prevalence was 4.5% (4/88), 12.1% (4/33), and 10.8% (4/37), respectively. The ADT-treated patients had significantly higher serum amino-terminal telopeptide levels than the hormone-naive patients (P = .014), but significantly lower serum carboxy-terminal telopeptide of type-I collagen levels than the ADT-treated patients with bone metastasis (P <.001). Our cross-sectional study confirmed that both ADT-treated and hormone-naive Japanese patients with prostate cancer have low rates of osteoporosis. These findings are different from those of studies in western countries. Genetic and hormonal or other environmental factors may result in population differences in the characteristics of prostate cancer and BMD.

Effect of combined Low-Dose Radon- and Hyperthermia Treatment (LDRnHT) of patients with ankylosing spondylitis on serum levels of cytokines and bone metabolism markers: a pilot study

Ankylosing Spondylitis (AS) is a rheumatic disease and almost 50% of the affected patients suffer from osteoporosis. The ratio of Receptor Activator of Nuclear Factor κB Ligand (RANKL) and Osteoprotegerin (OPG) has become an important marker to assess the status of systemic bone metabolism and has been shown to be dysregulated in AS patients. Combined Low-Dose Radon- and Hyperthermia Therapy (LDRnHT) causes pain reduction in patients with AS and induces the cytokine transforming growth factor-β1 (TGF-β1). TGF-β1 acts as an anti-inflammatory cytokine and influences the OPG/RANK/RANKL system. We therefore performed a study on 33 AS patients to investigate the effect of LDRnHT on serum levels of bone metabolism markers and cytokines involved in chronic inflammatory disorders. It is shown that TGF-β1, TNF-α, IL-6, OPG and RANKL levels significantly increased after LDRnHT and that the ratio of OPG over RANKL is significantly elevated.

Is there any requirement for celiac disease screening routinely in postmenapausal women with osteoporosis?

Screening studies indicate a prevalence of celiac disease (CD) of up to 1% in populations of European ancestry, yet the majority of cases remain undiagnosed. One of the common complication of CD is intestinal osteopathy or osteoporosis [bone mineral density (BMD) based diagnosis]. Available data regarding the prevalence of CD in the patients with osteoporosis are limited and controversial. The objective of this study was to perform serological testing to screen for CD among postmenopausal women with osteoporosis. We studied 192 postmenopausal women with low BMD with a mean age of 62.75 +/- 8.58 years. Among the patients, a total of 137 had osteoporosis and 55 had osteopenia. Venous blood samples were obtained for serological screening of CD and evaluation of bone metabolism. The serological screening protocol consisted of determining serum level of IgA antigliadin antibodies (AGA), IgG-AGA, IgA endomysial antibody (EMA), IgG-EMA. Subjects who were positive for both IgA-AGA and IgA-EMA were classified as having CD. Bone metabolism was evaluated by serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone, 25 (OH) vitamin D, osteocalcin, serum C-telopeptide cross-linked collagen type I levels. Of the 192 patients evaluated, only one (0.5%) was found to have positive for both IgA-AGA and IgA EMA tests and accepted as having CD. Prevelance of CD in postmenopausal women with low BMD (0.5%) did not differ from prevelance of CD in normal healthy population (0.3-1%). BMD values at proximal femur level were significantly lower in IgA-AGA (+) patients when compared to IgA-AGA (-) patients. However, the mean levels of bone metabolism markers were found similiar in both IgA-AGA (+) and (-) patients. In conclusion, the results of our study suggest that there is no need for routine screening of CD in postmenopausal women with osteoporosis.

Impact of Cinacalcet Hydrochloride on Bone Histology in Patients with Secondary Hyperparathyroidism

Serum parathyroid hormone (PTH) levels are effectively decreased by cinacalcet hydrochloride (HCl) in patients with secondary hyperparathyroidism. We assessed the impact of cinacalcet HCl on bone histology in these patients. Four hemodialysis patients with secondary hyperparathyroidism (intact PTH > or = 300 pg/mL) were treated with cinacalcet HCl with low-doses of vitamin D sterols as well as calcium-based phosphate binders for 52 weeks. Patients 1, 2, 3 and 4 were aged 55, 65, 61 and 70 years old, and the duration of hemodialysis in the patients was 84, 176, 125 and 216 months, respectively. Serum intact PTH, serum bone metabolism markers and bone histomorphometric parameters were determined before and after 52 weeks of the treatment. Serum intact PTH decreased from 1110, 880, 330 and 980 pg/mL to 233, 80, 88 and 116 pg/mL, respectively, in the four patients after 52 weeks of treatment with cinacalcet HCl. Serum levels of bone metabolism markers and all of the histomorphometric resorption parameters decreased in these patients. In particular, fibrosis volume decreased to 0% in all of the patients. Static formation parameters, including osteoblast surface and osteoid-related parameters, all decreased after the treatment, indicating an increase of mineralized bone volume during the treatment. Dynamic parameters except for activation frequency decreased after the treatment, indicating significant suppression of bone turnover. Cinacalcet HCl with low-doses of vitamin D sterols suppressed serum PTH with no significant changes of serum calcium levels. In addition, long-term administration of cinacalcet HCl improved hyperparathyroid bone diseases in patients with secondary hyperparathyroidism.

Bone mineral density in Japanese prostate cancer patients under androgen-deprivation therapy

Androgen-deprivation therapy (ADT) of patients with prostate cancer (PCa) is known to reduce bone mineral density (BMD). However, the most studies examined Caucasian or black patients and the effects of ADT on the bone metabolism of East Asians are unclear. Therefore, we performed a cross-sectional study to elucidate the influence of ADT on bone metabolism in Japanese patients. In total, 101 native Japanese patients with PCa were enrolled. They consisted of 58 ADT-treated and 43 hormone-naive patients. The BMD in the lumbar spine, total hip, and femoral neck was measured by dual energy X-ray absorptiometry and expressed in s.d. units relative to young adult men (T-score) or age-matched men (Z-score). Serum levels of bone metabolism markers were also measured. The BMDs at the three sites revealed that 2.3% (1/43) and 8.6% (5/58) of the hormone-naive and ADT-treated PCa patients had osteoporosis respectively, but this difference failed to achieve statistical significance (P=0.294). The two groups also did not differ significantly in their Z-scores of the three sites, and univariate and multivariate analyses indicated that ADT was not a significant risk factor for decreased BMD. In addition, a significant correlation between the duration of ADT and BMD was not observed for all three sites measured. However, the ADT-treated patients had significantly higher serum levels of N-terminal telopeptide of type I collagen (NTx) than the hormone-naive patients (P=0.017). To our knowledge, this is the first study to demonstrate the low prevalence of osteoporosis in both ADT-treated and hormone-naive Japanese PCa patients. Moreover, ADT did not significantly increase the prevalence of osteoporosis in this Japanese population.

Sevelamer Hydrochloride Improves Hyperphosphatemia in Hemodialysis Patients With Low Bone Turnover Rate and Low Intact Parathyroid Hormone Levels

Sevelamer improves hyperphosphatemia without increasing the calcium load. However, it remains unknown whether sevelamer restores bone metabolism in hemodialysis patients with low bone turnover osteodystrophy and hypoparathyroidism. We investigated the changes in serum intact parathyroid hormone (iPTH) and bone metabolic marker levels after replacing calcium carbonate with sevelamer in these patients. We also conducted stratified analysis based on patient background and multivariate analysis to determine the factors affecting these parameters. During sevelamer replacement therapy, serum calcium and phosphate concentrations, and the calcium phosphate product were measured at 0, 1, 3, and 6 months. Serum iPTH, bone alkaline phosphatase and osteocalcin concentrations were measured at 0 and 6 months. In hemodialysis patients (71 men and 46 women, 63 +/- 12 years old) serum calcium levels and the calcium phosphate product decreased significantly at 1 month. Serum iPTH, bone alkaline phosphatase and osteocalcin levels increased significantly at 6 months. Increases in serum iPTH concentrations were observed in all stratified groups. Significant increases in serum bone alkaline phosphatase and osteocalcin concentrations were found only in the relative hypoparathyroidism group (iPTH levels > or =51.5 pg/mL, the median pretreatment level). Multivariate analysis showed that the factors affecting change in serum iPTH level are baseline serum iPTH, baseline calcium level (> or =9.5 mg/dL), and dialysis duration of 10 years or longer. Sevelamer appears useful for the treatment of hyperphosphatemia in these patients. Particularly, in the relative hypoparathyroidism group, the iPTH secretory response is probably enhanced and bone turnover may have been improved as a result of reducing the calcium load.

Increased Levels of Urinary N-Telopeptide of Type I Collagen Correlate with Reduced Survival in Patients with Advanced Multiple Myeloma.

Staging systems such as those of Durie-Salmon and the International Staging System provide important prognostic insight for patients (pts) with multiple myeloma (MM) throughout the disease continuum. However, detailed evaluations of prognostic factors in pts with advanced MM and primary bone lesions have not been reported. Therefore, an exploratory analysis of data was conducted from a randomized trial in pts with bone disease from MM to assess prognostic factors for survival (n=282). Patients received standard antineoplastic therapy including a bisphosphonate (zoledronic acid 4 mg, n=184; pamidronate 90 mg, n=98) every 3 to 4 weeks for up to 24 months. Dichotomous variables included sex, race (white/other), narcotic analgesics (yes/no), Eastern Cooperative Oncology Group performance status (active/impaired), prior skeletal-related event (SRE; yes/no), and values with a defined upper limit of normal (creatinine, lymphocyte %, hemoglobin, serum glutamic-oxaloacetic transaminase, albumin, lactate dehydrogenase [LDH], and calcium). Continuous variables included age, weight, cancer duration, Functional Assessment of Cancer Therapy-General score, Brief Pain Inventory score, and bone markers (eg, urinary N-telopeptide of type I collagen [NTX], deoxypyridinoline). Paraprotein type was also included. Univariate and multivariate analyses were developed to determine relative risks (RR) for reduced survival associated with baseline variables using Cox regression models, and those that were not significant at the 5% level were removed by backward elimination to generate a reduced model. In the reduced multivariate model, advanced age (P=.001), non-immunoglobulin (Ig) G myeloma subtype (IgA [P=.001] or light chain/nonsecretory/IgM [P=.051]), history of SREs before study enrollment (P=.004), anemia (P=.022), high urinary levels of NTX (P=.017), high serum levels of LDH (P=.014), and low serum levels of albumin (P=.025) significantly correlated with reduced survival. Because NTX levels were a significant covariate, the correlation between baseline NTX and survival was assessed. Normal NTX (< 50 nmol/mmol creatinine) was associated with a significant 47% lower risk of death versus elevated NTX in pts who received zoledronic acid (n=210; RR=0.53; P=.026); it was associated with a 38% lower risk in the smaller population of pts who received pamidronate (n=108; RR=0.62; P=.135). After 3 months of bisphosphonate treatment, a 50% reduction in NTX was achieved in approximately 83% of patients with an elevated baseline NTX (median, 82.5 nmol/mmol creatinine) who were treated with zoledronic acid. However, the same NTX reduction at 3 months was achieved in only 67% of pts with an elevated baseline NTX (median, 80.0 nmol/mmol creatinine) who were treated with pamidronate. In these analyses, age, albumin, Igs, and anemia were identified as prognostic factors for reduced survival in pts with advanced MM. In addition, a history of SREs before study enrollment and elevated levels of bone metabolism markers—specifically NTX—were identified. Bisphosphonates can delay the onset of potentially life-limiting skeletal complications and reduce NTX levels. Therefore, studies are under way to investigate whether bisphosphonates can improve survival in this setting.

Effects of 22‐Oxacalcitriol and Calcitriol on PTH Secretion and Bone Mineral Metabolism in a Crossover Trial in Hemodialysis Patients With Secondary Hyperparathyroidism

The purpose of this crossover comparison study is to elucidate the differences between the effects of a novel calcitriol analog, 22-oxacalcitriol, and calcitriol on parathyroid hormone (PTH) and bone mineral metabolism in hemodialysis patients with secondary hyperparathyroidism (SHPT). Twenty-three patients with moderate to severe SHPT were included in a random 2 x 2 crossover trial with two vitamin D analogs (12 weeks for each treatment). Two patients withdrew during the run-in period for personal reasons. Serum electrolyte, bone metabolic marker, intact PTH (iPTH) and whole PTH (wPTH) levels were measured periodically. The primary endpoint measure was a decrease in serum iPTH level, and the secondary outcome measures included changes in serum calcium (Ca), phosphate (P), and metabolic bone marker levels. Both treatments decreased iPTH and wPTH levels by similar degrees. Serum Ca, P, and Ca x P product levels at the end of each treatment were comparable and the frequencies of hypercalcemia and hyperphosphatemia were also similar during each treatment period. 22-Oxacalcitriol significantly decreased the levels of bone metabolic markers, namely, bone-specific alkaline phosphate, intact osteocalcin, pyridinoline, and cross-linked N-telopeptide of type I collagen, after a 12-week treatment. In contrast, calcitriol did not change any of the levels of bone metabolic markers. The present study showed that 22-oxacalcitriol is equally effective for PTH suppression, and Ca and P metabolism. In addition, 22-oxacalcitriol might have putative actions on bone remodeling independent of its PTH suppression. Further study is necessary to confirm the effects of 22-oxacalcitriol on bone metabolism in SHPT.

Clinical Usefulness of the Measurement of Bone Mineral Content by Radiographic Absorptiometry in the Young Thoroughbred

The purpose of this investigation was to evaluate the clinical usefulness of the total radiographic bone aluminum equivalency (RBAE) method for the measurement of bone mineral content (BMC) in the third metacarpal bone (McIII) of the young Thoroughbred by examining: a) changes in BMC and bone metabolism marker levels in young Thoroughbreds being trained in the growth period; b) correlation of BMC and bone metabolism marker levels; and c) relationships of BMC and bone metabolism marker levels with the state of occurrence of bone disorders. The total RBAE method by the ortho system was chosen for this study. Ninety-one 2-year-old Thoroughbreds that showed no abnormalities on physical examination before the study were evaluated for BMC, and 39 were selected at random for evaluation of the bone metabolism marker levels. BMC of the normal horses showed no change between Days 0 and 90 of the study, but significantly increased on Day 180 (p<0.01). BMC showed no correlations with bone metabolism markers. In addition, there was a high incidence of bone disorders in Days 0-90 of the study when BMC did not change though training increased. These results suggest that the measurement of BMC by the total RBAE method in young Thoroughbreds is useful for providing information about skeletal development, and also for obtaining information on the predisposing period for bone disorders.

Bone metabolism markers predict increase in bone mass, height and sitting height during puberty depending on the VDR Fok1 genotype

Longitudinal growth and bone mass accumulation are two important phenomena during puberty, resulting in attainment of peak bone mass (PBM) and final height. They are thought to be under strong genetic control, with the vitamin D receptor (VDR) gene being among the candidate genes. Bone metabolism markers are reported to be good predictors of longitudinal growth and bone mass increase. The purpose of this longitudinal study was to evaluate whether bone metabolism markers predict bone mass and height increase differently according to Fok1 VDR genotype throughout puberty in healthy adolescents. At the start of the study 130 girls were aged 10.8 (range 8.5-12.8) years and 125 boys were aged 11.8 (range 9.4-14.6) years at the first visit. Markers of bone formation and bone resorption were measured at the first visit, as well as height and sitting height (SH), and bone mineral content (BMC) of the lumbar spine, femur, arm and total body. All measurements were repeated after 2 years. A higher BMC of the femur, distal arm and total body was found in ff boys at the first visit, which was not related to higher levels of bone metabolism markers in this group. In girls, no differences between genotypes were seen in BMC (increase). However, concentrations of markers of bone formation [alkaline phosphatase (AP), bone-specific alkaline phosphatase (BAP), procollagen aminoterminal propeptide (PINP)] and bone resorption [type I carboxyterminal telopeptide (ICTP)] were higher in ff girls. Regression coefficients between bone metabolism markers and bone mass increase differed according to genotype and sex. A similar pattern was found for height and SH (increase), the latter as a representative of growth of the axial skeleton, mainly consisting of cancellous bone. Our data suggest that the predicting capacities of bone metabolism markers on bone mass (increase), height and SH (increase) are genotype dependent. Their use as predictors of final height or PBM therefore remains questionable without knowing the genotype.

The serum level of bone-specific alkaline phosphatase activity is associated with aortic calcification in osteoporosis patients

It has been suggested that there are several possible linkages between vascular calcification and osteoporosis. In addition, the processes of vascular calcification may have a common etiology with bone formation. Thus, we hypothesized that the serum levels of bone metabolic markers would be different between osteoporosis patients with and without vascular calcification. In this study, we showed that the serum level of bone-specific alkaline phosphatase activity in osteoporosis patients with abdominal aortic calcification had a higher value than in those without the calcification. On the other hand, there were no significant differences in the urine levels of type I collagen cross-linked N-telopeptides (a bone resorption marker), or in the serum levels of intact osteocalcin, Ca, and P. Bone-specific alkaline phosphatase is the most important marker for osteoblast differentiation; furthermore, the serum level of its activity may reflect the process of calcification of the aorta in osteoporosis patients.

Effects of gonadotropin-releasing hormone agonists on bone metabolism markers and bone mineral density in patients with prostate cancer

Objectives To better understand bone metabolism and predict bone loss in treatment using gonadotropin-releasing hormone agonist for patients with prostate cancer. Methods The changes in bone mineral density and blood levels of bone metabolism markers and the level of pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen, a specific marker of bone resorption, and carboxy-terminal pro-peptide of human type I procollagen, a specific marker of bone formation, were examined in 27 consecutive patients with prostate cancer without bone metastasis. Results After 2 years of gonadotropin-releasing hormone treatment, the bone mineral density was significantly lower (median 0.937 g/cm 2) than before treatment. Pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen began to increase significantly 6 months after the start of treatment (3.0 to 8.3 ng/mL, median 4.6, at baseline versus 3.4 to 8.2 ng/mL, median 5.2, after 6 months). Carboxy-terminal pro-peptide of human type I procollagen began to show a significant rise 1 year after the start of treatment (from 72.8 to 221.5 ng/mL, median 102.0, at baseline to 82.7 to 293.4 ng/mL, median 132.0, at 1 year). Conclusions Functional coupling between bone resorption and formation was noted, and a decrease in bone mass, even in men, owing to androgen deficiency, was biochemically demonstrated. Fluctuations in these two bone metabolism markers preceded the decrease of bone mineral density. Therefore, these markers might be a predictor of bone loss.