Biochemical Markers Of Bone Metabolism Research Articles

Osteopenia in HIV-infected women prior to highly active antiretroviral therapy.

Multiple endocrine and metabolic consequences of human immunodeficiency (HIV) infection exist that alter bone metabolism in patients with acquired immune deficiency syndrome (AIDS). Osteopenia in AIDS patients has been associated with antiretroviral therapy particularly with protease inhibitors. However, there is very little data on bone metabolism in female subjects with AIDS prior to highly active antiretroviral therapy. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry (DEXA) in 50 HIV-infected female outpatients (mean age 37 years) both in the lumbar spine and the Ward's triangle of the left hip. Additional parameter assessed were demographics, smoking, CD4 counts, fasting metabolic parameters and biochemical markers of bone metabolism. None of the patients received reverse transcriptase inhibitors or protease inhibitors, vitamin D or calcium-supplementation. The serum levels of parathyroid hormone and 1,25-dihydroxyvitamin D (1,25(OH2)D) were significantly reduced compared to 50 age-matched female healthy controls. Urinary calcium and pyridinium crosslinks-excretion corrected for creatinine excretion were elevated (P<0.01) and were likewise significantly correlated with the loss of CD4 cells (P<0.05). Serum osteocalcin was significantly lowered (P<0.01). Reduced BMD of the lumbar spine (t -score <-2.5 SD below normal) was found in seven patients (14%) and osteopenia (t -score -1.0 to -2.5 SD below normal) was diagnosed in 31 (62%). No patient had a fracture since being infected with HIV. The BMD was reduced both in lumbar spine and the hip measured in the left Ward's triangle. There were significant positive correlation between the CD4 counts and 1,25(OH2)D (P<0.05). Neither the CD4 counts nor the duration of disease correlated with BMD. The reduced bone formation rate was linked to progressive loss of CD4-cell count. Osteopenia in HIV-infected female subjects is commonly manifested both in lumbar spine and Ward's triangle of the hip. There is a dissociation between lowered markers of bone formation rate and the increased bone resorption expressed as elevated urinary crosslinks and calcium excretion. Furthermore, the decreased levels of 1,25(OH2)D may contribute to a negative calcium balance and inhibition of bone formation. Our results suggest that further research is necessary to determine, whether low levels of 1,25(OH2)D lead to an accelerated inflammatory process in AIDS, since 1,25(OH)2D is known as an endogenous immune modulator suppressing formation of activated T cells and cell proliferation.

Calcium-sensing receptor gene polymorphism A986S does not predict serum calcium level, bone mineral density, calcaneal ultrasound indices, or fracture rate in a large cohort of elderly women.

Postmenopausal osteoporosis is a complex and heterogeneous disease influenced by multiple factors and related to peak bone mass achieved in early adult life, followed by a subsequent continuous bone loss. Genetic variance and polymorphisms have been shown to be of clinical significance for osteoporotic fragility fractures. Previous studies have related variations in the calcium sensor receptor (CASR) gene to circulating Ca levels and bone mass in young women and adolescent girls. The aim of this study was to investigate the impact of the A986S polymorphism of the CASR gene on calcium homeostasis and bone metabolism in elderly women. We studied the distribution of the A986S polymorphism in a large cohort of 1252 ambulatory Australian women in relation to biochemical markers of bone metabolism, bone mass evaluated by quantitative ultrasound measurements (QUS) and DXA of the hip, prevalent and 36-month incident fracture data. No effect of the polymorphism was found on circulating calcium level, renal Ca excretion, or biochemical markers of bone turnover. Moreover, A986S was not associated with bone mass or prevalent or incident fractures. Power calculations revealed that a difference in circulating calcium levels of 0.05 mmol/l, a difference in DXA bone density of 24 mg, and a 1.6-fold difference in fracture rate could have been detected with a power of 80%. In conclusion, in a large cohort of elderly women the A986S polymorphism of the CASR gene was not found to be significant for calcium homeostasis or bone mass. It is questioned whether the polymorphism has any clinical significance for postmenopausal osteoporosis.

Vitamin D receptor gene polymorphism and bone metabolism during low-dose oral contraceptive use in young women

With the aim to determine whether bone metabolism in young women using low-dose oral contraception is influenced by vitamin D receptor (VDR) genotype, we designed the prospective clinical study of 41 healthy women aged 20–27 years. Twenty-one women of the study group were prescribed an oral contraceptive (30 μg ethynyl estradiol and 150 μg levonorgestrel) and 20 women of the control group a nonhormonal contraceptive or none. Biochemical markers of bone metabolism (bone-specific alkaline phosphatase, osteocalcin, deoxypyridinoline) and VDR genotype, using BsmI endonuclease, were determined. After 3 months in the study group, the BB genotype subgroup showed significantly decreased osteocalcin (p = 0.010), in the Bb genotype subgroup bone-specific alkaline phosphatase (p = 0.043) and osteocalcin (p = 0.006) decreased, and in the bb genotype subgroup no changes were observed. In the control group, there were no significant changes in markers of bone metabolism regarding VDR genotype. In conclusion, our study shows that in young women VDR gene polymorphism could influence bone metabolism during low-dose oral contraceptive use.

Effects upon Bone Metabolism following Total Hip and Total Knee Arthroplasty

Objective: In a prospective study we evaluated the course of markers for bone formation and bone resorption in patients undergoing elective total hip and total knee arthroplasty due to osteoarthritis. The aim was to evaluate which changes in bone metabolism take place in the immediate postoperative course following arthroplasty. Methods: Serum and urine samples were obtained preoperatively and in the postoperative course from patients undergoing total arthroplasty over a 90- or 180-day period. The study included a total of 63 patients with cemented hip prostheses (n = 20), uncemented hip prostheses (n = 23) and cemented knee prostheses (n = 20). Different biochemical markers of bone metabolism were assessed including the serum markers bone-specific alkaline phosphatase, and carboxyterminal propeptide of type I procollagen, and the urine markers n-telopeptide (NTx) and deoxypyridinoline (DPD). Results: For all four markers, there were changes over time which were statistically significant. Markers indicating bone formation were slightly elevated after a 3-month period. In contrast, the two markers indicating bone resorption were back to normal after a 6-month period. There were differences between the groups with cemented and uncemented total hip arthroplasty in the postoperative course with higher values of the markers indicating bone resorption in the cemented group. However, these differences were not statistically significant. Conclusions: Our results indicate that the two markers of bone resorption, NTx and DPD, are elevated during the first 6 months after hip and knee arthroplasty. Therefore, during this period they cannot be used as a marker for aseptic loosening. However, if these two markers are still elevated after this period, they may reflect an impaired bone metabolism. Further studies are required to assess the potential value of these markers for the diagnosis of aseptic loosening.

Development of lumbar bone mineral density in the late course after kidney transplantation

Background: Rapid bone loss is a frequent finding early after kidney transplantation. Only limited data are available on the bone mineral density (BMD) in long-term kidney transplant recipients. Methods: In 26 kidney transplant recipients (13 men and 13 women, age 45.3 ± 12.3 years), serum biochemical markers of bone metabolism and BMD at the lumbar vertebrae L2-4 were evaluated prospectively in three serial examinations (E1, E2, E3; method: dual-energy X-ray absorptiometry). Examinations were performed at 47 ± 2 months, 59 ± 2 months, and 71 ± 2 months after transplantation. All patients received standard dual or triple immunosuppression including prednisolone. Results: The mean BMD was significantly lower (P < 0.001) than in sex-matched young controls: T-score was −1.43 ± 1.49 (E1), −1.39 ± 1.40 (E2), and −1.44 ± 1.30 (E3). The BMD did not change significantly (Δ BMD, −0.5 ± 5.9%) from E1 to E3. Regression analysis did not show significant associations between Δ BMD and biochemical parameters or prednisolone dosage. No clinically apparent new lumbar vertebral fracture occurred. The mean intact parathyroid hormone was 110.1 ± 97.5 pg/mL (E1), 121 ± 102.7 pg/mL (E2), and 134.5 ± 128.6 pg/mL (E3). Serum creatinine was 1.44 ± 0.45 (128 ± 40) mg/dL (μmol/L) (E1), 1.44 ± 0.47 (127 ± 42) mg/dL (μmol/L) (E2), and 1.45 ± 0.70 (128 ± 62) mg/dL (μmol/L) (E3). Ten patients (38.5%) showed an increase of BMD (+5.7 ± 3.2%) and 15 patients (57.7%) showed a decrease of −4.7 ± 3.2% (P < 0.0001). Both groups were different in T-scores at E1 (−2.29 ± 1 versus −0.88 ± 1.5); intact parathyroid hormone, creatinine, vitamin D levels, and prednisolone dosage were not significantly different. Conclusion: This study shows that lumbar BMD is reduced in long-term kidney transplant recipients. During our 24-month observation period, overall lumbar BMD remained stable. Am J Kidney Dis 40:1066-1074. © 2002 by the National Kidney Foundation, Inc.

Bone metabolism in advanced cholestatic liver disease: Analysis by bone histomorphometry

Despite the clinical importance of cholestatic osteopenia, little is known about its pathophysiologic mechanism. By tetracycline-labeled histomorphometric analysis of bone biopsies taken at the time of liver transplantation, we prospectively evaluated bone resorption and formation in 50 consecutive patients with advanced primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Histomorphometric analysis confirmed low bone volume parameters, consistent with the mean T-score of the lumbar spine of −1.9 by dual energy x-ray absorptiometry. Dynamic (bone formation rates, adjusted apposition rates) and static (osteoid markers, osteoblast number) parameters of bone formation were decreased in cholestatic patients with no abnormalities in mineralization. Increased osteoclast numbers and increased eroded surface areas suggested increased bone resorption, and this was supported in female patients by increased trabecular separation and decreased trabecular number. Male cholestatic patients, however, did not have significant increases in resorption parameters, although they were as osteopenic as female patients and had low bone formation markers. Bone histomorphometric changes were similar in PBC and PSC, suggesting an etiologic effect of chronic cholestasis rather than the individual diseases. Cancellous bone volume and osteoid markers correlated with bone mineral density measurements but no correlations were found between histomorphometric parameters and biochemical markers of bone metabolism. In conclusion, cholestatic osteopenia appears to result from a combination of decreased bone formation and increased resorption, especially in female patients, but the relative importance of these two abnormalities and their actual etiology remain to be elucidated. (H EPATOLOGY 2002;36:895-903.)

Evaluation of bone disease in multiple myeloma: a correlation between biochemical markers of bone metabolism and other clinical parameters in untreated multiple myeloma patients

Introduction: Multiple myeloma (MM) is characterised by an uncoupled bone formation/resorption process resulting in osteolysis. Osteocalcin (OC) and bone-specific alkaline phosphatase (BAP) are markers of osteoblastic activity, whereas pyridinoline products and the cross-linked aminoterminal of type I collagen (NTx) reflect bone destruction. In this study, these markers were studied in relation to bone disease severity and other clinical parameters of MM activity. Methods: Serum calcium, creatinine, CRP, beta 2 microglobulin (b 2M), M-component, OC, BAP and free urine pyridoline (Pyd) and deoxypyridinoline (Dpd), free urine Dpd and NTx were determined in 38 newly diagnosed MM patients. X-ray examination defined the degree of bone involvement. Patients were classified according to the Durie–Salmon staging system. Results: NTx, free urine Pyd+Dpd, and free urine Dpd increased with increasing degree of bone involvement. NTx was significantly higher in stages II and III compared to stage I (mean values: 100.7, 163.5 and 208.3 nmol BCE/mM creat, respectively, p<0.002). Free urine Pyd+Dpd correlated positively with b 2M and CRP. OC was increased in stages I and II compared to III ( p<0.005) and was inversely correlated with NTx, free urine Pyd+Dpd, and free urine Dpd alone. Conclusions: The measurement of bone turnover markers in MM provides significant information regarding disease progression and should be included in the evaluation of MM patients.

Biochemical markers of bone metabolism in relation to adrenocortical and growth suppression during the initiation phase of inhaled steroid therapy.

Growth suppression is usually most evident during the first year of inhaled steroid therapy. Steroid-induced changes in bone metabolism may contribute to this growth suppression. The aim of the present study was to evaluate the changes in biochemical markers of bone metabolism in relation to adrenal and growth suppression during the initiation phase of inhaled steroid therapy. Seventy-five school-aged children with new asthma were enrolled into budesonide (BUD, n = 30), fluticasone propionate (FP, n = 30) or cromone (CROM, n = 15) treatment groups. BUD dose was 800 microg/d during the first two months and 400 microg/d thereafter. The respective FP doses were 500 and 200 microg/d. Biochemical markers of bone metabolism were measured before treatment and after 2 and 4 mo of therapy. In the control (CROM) group, the mean concentrations of serum osteocalcin (OC), carboxyterminal propeptide of type I procollagen (PICP) (formation markers) and type I collagen carboxyterminal telopeptide (ICTP) (degradation marker) tended to increase. In the BUD group, OC and PICP decreased during the 4 mo by a mean of 23% (p < 0.001) and 15% (p < 0.05), respectively, while ICTP did not change significantly. In the FP group, OC and ICTP decreased during the first 2 mo by a mean of 19% (p < 0.01) and 21% (p < 0.01), respectively, returning to the pretreatment level at 4 mo, while PICP tended to increase during the 4 mo (14%, p = 0.12). In the steroid treated children whose height SD score decreased during the first 12 mo of therapy, both OC and PICP decreased during the first 4 mo by a mean of 20% (p < 0.01) and 21% (p < 0.001), respectively. In those children who had no growth suppression, the changes were not significant: -4% in OC and +13% in PICP. Furthermore, in children who developed evidence of adrenocortical suppression (on the basis of a low-dose ACTH test), OC decreased more (23%, p < 0.01) than in those with normal adrenocortical function (10%, p = 0.06). In conclusion, both inhaled BUD and FP caused dose-dependent effects on biochemical markers of bone metabolism. The children who developed growth or adrenocortical suppression were likely to have changes also in bone metabolism.

Biochemical Markers of Bone Metabolism in Relation to Adrenocortical and Growth Suppression During the Initiation Phase of Inhaled Steroid Therapy

Growth suppression is usually most evident during the first year of inhaled steroid therapy. Steroid-induced changes in bone metabolism may contribute to this growth suppression. The aim of the present study was to evaluate the changes in biochemical markers of bone metabolism in relation to adrenal and growth suppression during the initiation phase of inhaled steroid therapy. Seventy-five school-aged children with new asthma were enrolled into budesonide (BUD, n = 30), fluticasone propionate (FP, n = 30) or cromone (CROM, n = 15) treatment groups. BUD dose was 800 μg/d during the first two months and 400 μg/d thereafter. The respective FP doses were 500 and 200 μg/d. Biochemical markers of bone metabolism were measured before treatment and after 2 and 4 mo of therapy. In the control (CROM) group, the mean concentrations of serum osteocalcin (OC), carboxyterminal propeptide of type I procollagen (PICP) (formation markers) and type I collagen carboxyterminal telopeptide (ICTP) (degradation marker) tended to increase. In the BUD group, OC and PICP decreased during the 4 mo by a mean of 23% (p < 0.001) and 15% (p < 0.05), respectively, while ICTP did not change significantly. In the FP group, OC and ICTP decreased during the first 2 mo by a mean of 19% (p < 0.01) and 21% (p < 0.01), respectively, returning to the pretreatment level at 4 mo, while PICP tended to increase during the 4 mo (14%, p = 0.12). In the steroid treated children whose height SD score decreased during the first 12 mo of therapy, both OC and PICP decreased during the first 4 mo by a mean of 20% (p < 0.01) and 21% (p < 0.001), respectively. In those children who had no growth suppression, the changes were not significant: −4% in OC and +13% in PICP. Furthermore, in children who developed evidence of adrenocortical suppression (on the basis of a low-dose ACTH test), OC decreased more (23%, p < 0.01) than in those with normal adrenocortical function (10%, p = 0.06). In conclusion, both inhaled BUD and FP caused dose-dependent effects on biochemical markers of bone metabolism. The children who developed growth or adrenocortical suppression were likely to have changes also in bone metabolism.

Bone mineral density and fracture prevalence in long-term kidney graft recipients.

Renal transplantation triggers an early bone loss that increases the subsequent risk of osteoporosis and fractures. Little is known about the long-term outcome of bone status and fracture prevalence several years after transplantation. Therefore, we conducted a cross-sectional evaluation of bone status to find out the frequency and predictors of osteoporotic fractures in late kidney graft patients. Changes in spinal, hip, and total body bone mineral density were assessed using a DEXA Hologic QRD 1000 scanner, and fractures were quantified in all kidney graft patients presenting for routine evaluation with a minimal follow-up of 5 years after transplantation (with a mean follow-up 8.5+/-3.1 years). We measured biochemical markers of bone metabolism and collected clinical and dietary intake data. Fifty-nine renal graft recipients were enrolled in the study within 9 months. Osteoporosis, according to the World Health Organization definition, was observed in 31 patients (53% of the total population) and fractures occurred in 26 patients (44% of the total population and 51.6% of patients with osteoporosis). Femoral neck bone mineral density was positively correlated with patient's weight and cyclosporin current dosage. Steroid cumulative dosage correlated only to lumbar spine Z score. Dietary calcium, serum 25 hydroxyvitamin D, parathyroid hormone, and urinary N-telopeptides excretion were normal. These data emphasize the substantial prevalence of osteoporosis and fractures among very long-term kidney graft recipients. Therapeutic intervention in these patients is urgently needed.

Additive Effects of Raloxifene and Alendronate on Bone Density and Biochemical Markers of Bone Remodeling in Postmenopausal Women with Osteoporosis

More skeletal benefit has reportedly been achieved using two antiresorptive treatments in combination, presumably because these treatments have different mechanisms of action. Bisphosphonates such as alendronate (ALN) bind to hydroxyapatite and inhibit bone resorption by reducing osteoclast numbers and activity. The selective estrogen receptor modulators, including raloxifene (RLX), act in a tissue-specific manner by binding to estrogen receptors and then to target genes, modifying gene expression. This study examined the results of these two agents, alone and in combination, compared with placebo. Lumbar spine and femoral neck bone mineral density (BMD) were estimated, and biochemical markers of bone metabolism determined in 331 postmenopausal women with established osteoporosis. Using a randomized double-blind design, the participants were given placebo, RLX in a dose of 60 mg daily, 10 mg daily of ALN, or both active treatments in combination for 12 months. The study was completed by 274 women, with no differences in baseline characteristics among the treatment groups. After 12 months, BMD in both the lumbar spine and femoral neck was significantly greater than at baseline in all treatment groups (Fig. 1), and also significantly more than in placebo recipients. Spinal BMD increased significantly more in patients given ALN alone than in the RLX group. Femoral BMD improved more with combination treatment than in patients given RLX only. All biochemical markers of bone turnover decreased from baseline after 12 months in the study, and all differed from placebo values (Fig. 2). The declines in bone marker levels were comparable in the ALN and combination treatment groups, but were more marked in both of these groups than with RLX alone. Additional analysis suggested that RLX and ALN act independently on BMD, and that the effects are additive. There were no substantial differences in rates of adverse effects among the group, and withdrawal rates did not differ significantly. A combination of ALN and RLX increased BMD more than either agent alone in this trial, conducted in postmenopausal women with osteoporosis. The effects of combined treatment on the risk of fracture remain unknown, as is the long-term clinical safety of combination therapy.

Bone mass, bone metabolism, gonadal status and body mass index.

Weight and gonadal status are the main determinants of bone mass in women. Because of this it is important to study which influences it more. The effect of weight (expressed as body mass index, BMI) and gonadal status of women on total-body bone mineral content (TBBMC) and regional bone mineral content (BMC) was investigated. A total of 373 normal women (mean age 48.9 +/- 13.4 years) were studied: 171 postmenopausal women (mean age 59.3 +/- 9.5 years; years since menopause 11.3 +/- 6.7 years); 76 perimenopausal women (mean age 48.9 +/- 2.2 years); and 126 premenopausal women (mean age 34.7 +/- 7.4 years). In all the women, TBBMC and regional BMC were determined by dual-energy X-ray absorptiometry. Also biochemical markers of bone metabolism (total alkaline phosphatase and tartrate-resistant acid phosphatase) and serum estrone and estradiol were determined. When the women were stratified by gonadal status and BMI, thin women (BMI <20 kg/m2) had significantly lower TBBMC and regional BMC, lower gonadal steroid concentration and higher levels of biochemical markers than overweight (BMI 25-30 kg/m2) and obese (BMI >30 kg/m2) women, regardless of gonadal status. Overweight and obese women had findings suggestive of increased parathyroid activity, but greater bone mass. Weight rather than gonadal steroid concentration is the main determinant of bone mass in women regardless of gonadal status.

Age- and gender-related differences in bone mineral status and biochemical markers of bone metabolism in Northern Chinese men and women

The aim of this study was to provide insight into the bone mineral status and biochemical markers of bone metabolism in a Chinese population from Shenyang, in the north of China, where hip fracture incidence is low. A total of 194 healthy men and women, aged 25–35 years and 65–75 years, were studied. Bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN) was measured using dual-energy X-ray absorptiometry. Fasting blood and 24 h urine samples were collected for bone alkaline phosphatase (bAP), osteocalcin, calcium, phosphate, and free deoxypyridinoline (Dpd). Both older women and men had lower BMD compared with younger women and men by 27.2 ± 3.0% (mean ± SE) and 9.8 ± 3.0% at the LS and 22.0 ± 3.4% and 12.8 ± 3.4% at the FN, respectively, after adjusting for bone and body size ( p < 0.01). BMD at the two sites was lower in older women than in older men by 10.7 ± 4.1% and 10.2 ± 4.2%, respectively, after size correction ( p < 0.05). Plasma bAP, osteocalcin, calcium, and phosphate concentrations were higher in older women than younger women by 69.3 ± 9.7%, 77.2 ± 11.1%, 7.5 ± 2.3%, and 8.0 ± 3.8%, respectively, and older men by 67.6 ± 11.1%, 72.1 ± 11.0%, 7.7 ± 2.3%, and 23.8 ± 3.8%, respectively ( p < 0.01). However, plasma osteocalcin, calcium, and phosphate concentrations were lower in older men compared with their younger counterparts by 35.6 ± 11.0%, 8.7 ± 2.3%, and 14.1 ± 3.8%, respectively ( p < 0.05). Urinary calcium and phosphate output were lower in older men compared with younger men by 48.0 ± 10.3% and 27.6 ± 6.9%, respectively ( p < 0.01), whereas there were no differences between older and younger women. No differences in Dpd between older and younger groups were found. This study demonstrates that bone mineral status is lower in older people in Shenyang, as has been shown in populations elsewhere. The pronounced low bone mineral status in older women may be associated with increased bone turnover, which was not observed in older men.

Bone metabolism and bone mineral density in premenopausal women with mild depression.

This study was undertaken to investigate the bone metabolism and bone mineral density (BMD) in female patients suffering from depression. Forty-two female patients diagnosed with depression and 42 healthy women, all in the premenopausal age, were enrolled. A clinical evaluation, measurements of the biochemical markers of bone metabolism and BMD measurements were performed. The BMD values were found to be similar in all measured sites. It was concluded that a low BMD was not a prominent feature of premenopausal women with mild depression, even though an increase in bone resorption was found.

Vitamin D Status, Parathyroid Hormone and Bone Mineral Density in Patients with Inflammatory Bowel Disease

Background: Although the pathogenesis of osteoporosis in inflammatory bowel disease (IBD) is not established, vitamin D deficiency and disturbances in calcium metabolism are thought to be of importance, especially in Crohn disease (CD). Vitamin D status is assessed and the relation between indices of calcium metabolism, including 25-hydroxyvitamin D and parathyroid hormone concentrations, and bone mineral density (BMD) in CD and ulcerative colitis (UC) are examined. Sixty patients with CD and 60 with UC were investigated. Each group comprised 24 men and 36 women. Methods: Vitamin D metabolites, parathyroid hormone and biochemical markers of bone metabolism were measured in blood and urine. Lumbar spine, femoral neck and total body BMD were measured by dual X-ray absorptiometry (DXA) and Z-scores were obtained by comparison with age- and sex-matched normal values. Results: Vitamin D deficiency (25-hydroxyvitamin D3 <30 nmol/l) was present in 27% of patients with CD and in 15% with UC. Furthermore, CD patients had a significantly lower mean concentration of 25-hydroxyvitamin D3 compared with UC patients. Vitamin D status was not related to BMD at any of the skeletal sites measured. Secondary hyperparathyroidism was found in 10 out of 27 patients with CD after small-bowel resections. No differences were found in serum osteocalcin and urine pyridinoline between patients with CD and those with UC. Conclusions: Hypovitaminosis D is common in CD patients. Patients with CD and small-bowel resections are at risk of developing secondary hyperparathyroidism and low BMD.

Calcium Bioavailability in Relation to Bone Health

A well established stable isotope technique exists for measuring calcium absorption from single foods and meals, but the long term effects of calcium on bone health cannot be assessed from acute bioavailability studies. Bone health depends primarily on the degree of mineralization, measured as bone mineral density (BMD), and phenotypic variations depend on genetic and environmental factors including calcium supply. Since almost all retained calcium is used for bone mineralization and remodeling, BMD can be used as a long-term (> six months) marker of dietary calcium bioavailability. However, BMD is a very insensitive marker of calcium bioavailability, so its use in dietary intervention studies is restricted to periods of significant bone growth or loss. Biochemical markers of bone metabolism may be used to predict the overall bioavailability of dietary calcium over a shorter time period (> four weeks), but they have a high coefficient of variation, so may not be appropriate for some dietary intervention studies. A group of European laboratories is currently developing an alternative approach using a long-lived radioisotope (41Ca) to label bone calcium and to directly measure the rate of calcium loss from urinary excretion data. The efficiency of calcium absorption is inversely related to intake; whole body balance of the mineral is dependent on rates of absorption and excretion and limited by calcium-binding substances in the gut. Dietary data and indirect measures of bone health indicate that bioavailability is important when habitual intakes are low, especially during periods of bone growth or loss. Further research is required to quantify the effects of major dietary modulators of calcium balance on bone health and to understand their relationship with genetic and physiological variables.

Osteoporosis screening in systemic lupus erythematosus: impact of disease duration and organ damage.

The aim of the present study was to assess the effects of disease severity and demonstrable organ damage as risk factors for the development of osteoporosis in systemic lupus erythematosus (SLE). Sixty-four SLE patients were included. Mean disease duration was 7.7 +/- 5.7 y. Thirty-two patients had persistent organ damage, defined as SLICC-ACR damage score > or = 1. Disease activity measured by SLAM-2 ranged from 3 to 27. Bone mineral density (BMD) measurements were performed with dual X-ray absorptiometry. In addition, biochemical markers of bone metabolism were studied. BMD was inversely correlated with disease duration, damage score and cumulative glucocorticoid intake, but no correlation was found for current glucocortioid use or with markers of bone metabolism. In a multivariate analysis, body weight, disease duration and damage index fitted best for the prediction of BMD at both lumbar spine and femoral neck. Seven out of 64 patients had osteoporosis according to WHO criteria. In conclusion, severe osteoporosis is uncommon in lupus patients. Disease activity and severity were no major risk factors for loss of BMD in this study, but persistent non-bone-related organ damage was significantly linked to the presence of osteoporosis measured as decreased BMD. Our data suggest that, in addition to patients receiving glucocorticoids, patients with an SLICC-ACR > or = 1 or a disease duration > or = 7 y might benefit from regular monitoring of BMD as secondary prevention of damage.

Impaired secretion of parathyroid hormone is coherent to diabetic hemodialyzed patients

Diabetic bone disease is characterized by low bone turnover resulting from impaired secretion of parathyroid hormone (PTH). However, it was suggested that the difference in duration of hemodialysis (HD) therapy and age of patients between HD patients with and without diabetes mellitus (DM) may be responsible for a significant reduction in serum intact PTH (iPTH) level in HD patients with DM. The present study showed that although such major factors affecting PTH secretion as age, sex, HD duration, and serum calcium, phosphate, and magnesium levels did not differ significantly between HD patients with and without DM, serum iPTH levels were still significantly lower in HD patients with than without DM. Among biochemical markers for bone metabolism, serum levels of intact osteocalcin (iOC) and deoxypyridinoline (DPD) were significantly lower in HD patients with than without DM, whereas serum bone-specific alkaline phosphatase, pyridinoline, and β-crosslaps did not differ significantly between the two groups of patients. In summary, our findings indicate that PTH secretion may be significantly impaired in HD patients with DM compared with those without DM, and serum iOC and DPD are bone markers sensitive enough to detect low bone turnover in HD patients with DM. © 2001 by the National Kidney Foundation, Inc.

Cross-sectional evaluation of bone metabolism in men.

There are relatively few data concerning age-related changes of bone turnover in men. The aim of the study was to evaluate age-related changes of the levels of serum and urinary biochemical markers of bone metabolism in a large cohort of 934 men aged 19-85 years and to investigate their association with bone mineral density (BMD). Bone formation was evaluated using serum levels of osteocalcin (OC), bone alkaline phosphatase (BAP), and N-terminal extension propeptide of type I collagen (PINP). Bone resorption was evaluated by measurement of urinary excretion of beta-isomerized C-terminal telopeptide of collagen type I beta-CTX) of free deoxypyridinoline (fDpyr) and total Dpyr (tDPyr) and of the serum level of beta-CTX. Levels of biochemical bone markers were very high in young men and decreased rapidly until the age of 40 years and then more slowly until 60 years of age. After the age of 60 years, markers of bone formation remained stable while resorption markers showed a moderate and variable increase with aging. Serum and urinary beta-CTX levels were elevated only in about 5% of elderly men. The age-related increase of urinary excretion of tDpyr and of its free and peptide-bound fractions was related to the presence of elevated levels in a subgroup of about 15% of elderly men. Before 60 years of age, levels of biochemical bone markers were not correlated with BMD, whereas after 60 years of age, they were correlated negatively with BMD. After adjustment for age and body weight, BMD in men with the highest levels of biochemical bone markers (i.e., in the upper quartile) was 1.8-12.5% (i.e., 0.25-0.89 SD) lower than in men with levels of biochemical bone markers in the lowest quartile. In conclusion, bone turnover in men is high in young adults and decreases to reach a nadir at 55-60 years of age. After the age of 60 years, bone resorption markers--but not bone formation markers--increase in some men and are associated with lower BMD, suggesting that this imbalance is responsible for increasing bone loss in elderly men.

Fetal bone metabolism in normal and rhesus isoimmunised pregnancies.

To construct gestation-specific reference intervals for fetal concentrations of biochemical markers of bone metabolism and assess the effect of rhesus isoimmunisation on these. Fetal blood samples were obtained by cordocentesis from 175 pregnancies (43 complicated by rhesus isoimmunisation) and assayed for carboxy terminal pro-peptide of type I pro-collagen (PICP) and cross-linked carboxyterminal telopeptide of type I collagen (ICTP) which directly monitor the rate of bone formation and resorption respectively. Both plasma PICP and ICTP were negatively correlated with gestational age (r = -0.351 and -0.472 for PICP and ICTP, respectively, and P < 0.001 for both). In fetuses affected by rhesus isoimmunisation PICP levels were lower (P=0.030) and more variable (P <0.001) than expected, compared with normal unaffected fetuses. However, no such differences were found in the ICTP levels. In the fetuses affected by rhesus isoimmunisation there was a significant correlation between haemoglobin concentration and both PICP (r = 0.504, P = 0.001) and ICTP (r = 0.343, P = 0.030). Fetal bone turnover declines from early second trimester to term, and may be deranged in fetuses affected by rhesus isoimmunisation.