Evaluation of bone disease in multiple myeloma: a comparison between the resorption markers urinary deoxypyridinoline/creatinine (DPD) and serum ICTP, and an evaluation of the DPD/osteocalcin and ICTP/osteocalcin ratios.

Markers of bone metabolism were measured in 73 newly diagnosed myeloma patients and in age-matched controls. Correlations to bone disease on X-rays and survival were performed. In urine deoxypyridinoline/creatinine (DPD) and in serum carboxyterminal pyridinoline cross-linked telopeptide of type I collagen (ICTP), procollagen type I carboxy-terminal extension peptide (PICP) and osteocalcin were analyzed. The ratios DPD/osteocalcin and ICTP/osteocalcin were calculated. Skeletal X-ray findings were divided into no, limited and extensive bone involvement. DPD and ICTP levels were significantly elevated in patients compared to controls. Levels increased with advancing skeletal involvement. Serum osteocalcin was elevated in patients without visible bone disease. The level decreased with more advanced bone involvement. The finding of significantly elevated osteocalcin and ICTP levels in patients without bone involvement on X-rays indicates that bone markers might reflect bone disease better than X-rays in untreated myeloma patients. Ratios between bone resorption and bone formation markers added no further information on bone disease or survival. Only ICTP had prognostic value with an inverse correlation between serum levels and survival.     

Pegvisomant-induced serum insulin-like growth factor-I normalization in patients with acromegaly returns elevated markers of bone turnover to normal

Active acromegaly is associated with increased biochemical markers of bone turnover. Pegvisomant is a GH receptor antagonist that normalizes serum IGF-I in 97% of patients with active acromegaly. We evaluated the effects of pegvisomant-induced serum IGF-I normalization on biochemical markers of bone and soft tissue turnover, as well as levels of PTH and vitamin D metabolites, in 16 patients (nine males; median age, 52 yr; range, 28-78 yr) with active acromegaly (serum IGF-I at least 30% above upper limit of an age-related reference range). Serum procollagen III amino-terminal propeptide (PIIINP) and type I procollagen amino-terminal propeptide, osteocalcin (OC), bone-related alkaline phosphatase, C-terminal cross-linked telopeptide of type I collagen (CTx), albumin-corrected calcium, intact PTH, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D [1,25-(OH)(2) vit D], urinary type 1 collagen cross-linked N-telopeptide/creatinine ratio, and urinary calcium (24 h collection) were measured (single-batch analysis) at study entry and after IGF-I normalization, along with sera from 32 age- and sex-matched controls. Compared with controls, PIIINP, OC, and CTx were significantly elevated in patients at baseline. Pegvisomant-induced serum IGF-I normalization (699 +/- 76 to 242 +/- 28 micro g/liter, P < 0.001) was associated with a significant decrease in PIIINP, markers of bone formation (type I procollagen amino-terminal propeptide, OC, and bone-related alkaline phosphatase), and resorption (CTx and urinary type 1 collagen cross-linked N-telopeptide/creatinine ratio). 1,25-(OH)(2) vit D decreased and intact PTH increased significantly, but 25-hydroxy vitamin D was unaffected. A significant decline in calculated calcium clearance was observed. The decrease in serum IGF-I correlated positively with the decrease of serum PIIINP (r = 0.7, P < 0.01). After normalization of serum IGF-I, there was no statistical difference between patients and controls for any parameters for which control data were available. In conclusion, GH excess is associated with increased bone and soft tissue turnover. Pegvisomant-induced normalization of serum IGF-I results in a decrease in markers of bone and soft tissue turnover to levels observed in age-matched controls, and these changes are accompanied by an increase in PTH and a decrease in 1,25-(OH)(2) vit D. These data provide further evidence of the effectiveness of pegvisomant in normalizing the altered biological effects of GH hypersecretion.     

骨硬化蛋白:一个治疗骨质疏松的新靶点

高骨量疾病骨硬化症(sclerosteosis)和Van Buchem病由SOST基因表达缺失导致.由于SOST基因突变导致骨硬化蛋白不能表达或功能缺陷,可造成该病患者的过度骨形成,其作用机制与抑制Wnt信号转导通路相关.骨硬化蛋白通过与该通路共受体LRP5/6结合来阻断Wnt通路,进而对成骨细胞分化及矿化起抑制作用.由于骨硬化蛋白在抑制骨形成起关键作用且仅在骨组织表达,其单克隆抗体可用于治疗低骨量疾病如骨质疏松.     

Responses of markers of bone and collagen turnover to exercise, growth hormone (GH) administration, and GH withdrawal in trained adult males

To examine the interactions between acute exercise and GH on markers of bone and collagen turnover and to assess the potential for detecting GH abuse in athletes using these markers, we studied 17 aerobically trained males (age, 26.9+/-1.5 yr). Sequential studies of exercise, GH administration, and GH withdrawal were undertaken. A randomized, controlled study of rest vs. exercise showed that exercise did not change serum osteocalcin; other markers of formation increased transiently (each P<0.001): bone-specific alkaline phosphatase (+16.1%), carboxyterminal propeptide of type I procollagen (+14.1%), and procollagen III N-terminal extension peptide (+5.0%). The carboxyterminal cross-linked telopeptide of type I collagen, a bone resorption marker, increased 9.7% (P = 0.018) in response to exercise. A randomized, double blind, placebo-controlled, parallel study of recombinant human GH treatment (0.15 IU/kg x day) for 1 week increased serum osteocalcin (net increase preexercise, +/-10.0%; P = 0.017), carboxyterminal propeptide of type I procollagen (+17.6%; P = 0.002), procollagen III N-terminal extension peptide (+48.4%; P = 0.001), and carboxyterminal cross-linked telopeptide of type I collagen (53.3%; P = 0.009). Disappearance half-times after cessation of recombinant human GH for pre- and postexercise markers ranged from 248-770 h. We conclude 1) endurance exercise transiently activates bone and collagen turnover; 2) brief GH administration results in similar but quantitatively greater augmentation; and 3) these data will assist in designing a GH detection strategy.     

Gastric bypass surgery for morbid obesity leads to an increase in bone turnover and a decrease in bone mass

Little is known about the effects on the skeleton of laparoscopic Roux-en-Y gastric bypass (LRGB) surgery for morbid obesity and subsequent weight loss. We compared 25 patients who had undergone LRGB 11 +/- 3 months previously with 30 obese controls matched for age, gender, and menopausal status. Compared with obese controls, patients post LRGB had significantly lower weight (92 +/- 16 vs. 133 +/- 20 kg; P < 0.001) and body mass index (31 +/- 5 vs. 48 +/- 7 kg/m(2); P < 0.001). Markers of bone turnover were significantly elevated in patients post LRGB compared with controls (urinary N-telopeptide cross-linked collagen type 1, 93 +/- 38 vs. 24 +/- 11 nmol bone collagen equivalents per mmol creatinine; and osteocalcin, 11.6 +/- 3.4 vs. 7.6 +/- 3.6 ng/ml; both P < 0.001). Fifteen patients were studied prospectively for an average of 9 months after LRGB. They lost 37 +/- 9 kg and had a 29 +/- 8% fall in body mass index (both P < 0.001). Urinary N-telopeptide cross-linked collagen type 1 increased by 174 +/- 168% at 3 months (P < 0.01) and 319 +/- 187% at 9 months (P < 0.01). Bone mineral density decreased significantly at the total hip (7.8 +/- 4.8%; P < 0.001), trochanter (9.3 +/- 5.7%; P < 0.001), and total body (1.6 +/- 2.0%; P < 0.05), with significant decreases in bone mineral content at these sites. In summary, within 3 to 9 months after LRGB, morbidly obese patients have an increase in bone resorption associated with a decrease in bone mass. Additional studies are needed to examine these findings over the longer term.     

Prevention of bone loss in survivors of breast cancer: A randomized, double-blind, placebo-controlled clinical trial

BACKGROUND: Few data are available on the safety and efficacy of once-weekly oral bisphosphonate therapy in breast cancer survivors. OBJECTIVE: Our objective was to determine whether risedronate, 35 mg weekly, is efficacious and safe in preventing bone loss associated with chemotherapy-induced menopause. DESIGN: The study was a randomized, double-blind, placebo-controlled clinical trial over 12 months. SETTING AND PARTICIPANTS: Participants included 87 newly postmenopausal women with status post chemotherapy, recruited from a breast cancer clinic in an academic medical center. INTERVENTION: Participants were randomly assigned to receive risedronate 35 mg/wk or placebo. MAIN OUTCOME MEASURES: The primary outcomes were the 12-month changes in spine and hip bone mineral density. Secondary outcomes included changes in markers of bone resorption (urine N-telopeptide cross-linked collagen type I) and formation (osteocalcin, N-terminal propeptide of type I procollagen, and bone-specific alkaline phosphatase). RESULTS: After 12 months, bone mineral density increased by 1.2% at the spine and 1.3% at the hip in women on risedronate vs. significant decreases for women in the placebo group of 0.9% at the spine and 0.8% at the hip (P < 0.01, difference between groups). N-telopeptide cross-linked collagen type I, a marker of bone resorption, decreased by 19.3%, and N-terminal propeptide of type I procollagen, a marker of bone formation, decreased by 26.6% in participants on active therapy compared with increases in the control group. Risedronate was well tolerated, and the retention rate was 95% at 1 yr. CONCLUSIONS: Risedronate once weekly prevented bone loss and reduced bone turnover in women with breast cancer treated with chemotherapy. Early measures to prevent bone loss should be considered in this cohort of breast cancer survivors.     

Chronic idiopathic neutropenia of adults is associated with decreased bone mineral density and alterations in bone turnover biochemical markers.

The aim of this study was to assess bone mineral density (BMD) and biochemical indices of bone metabolism in patients with chronic idiopathic neutropenia of adults (CINA) and define the relationships, if any, between these parameters and serum levels of interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha), two cytokines normally involved in bone metabolism. Femoral neck BMD, serum osteocalcin (OC), bone-specific alkaline phosphatase (BAP) and type I procollagen carboxy-terminal propeptide (PICP), as well as urine-free deoxypyridoline (Dpd) cross-links, N-telopeptide (NTx) and C-telopeptide (CTx) cross-links of type I of collagen were measured in 45 CINA patients and 36 normal subjects. Patients were arbitrarily classified in two groups, A and B, as having mild (neutrophils 1700-2500/microl) or 'pronounced' (neutrophils<1700/microl) neutropenia, respectively. BMD values were found significantly reduced in both groups of patients, compared to controls, and they strongly correlated with the number of circulating neutrophils. Serum OC and urinary NTx were significantly increased in patients of group B. Both serum OC and urinary NTx correlated inversely with the number of circulating neutrophils. Serum BAP and PICP and urine Dpd and CTx were within normal range. Serum IL-1beta and TNF-alpha were elevated in both groups of patients and correlated inversely with the number of circulating neutrophils and the values of BMD. In addition, TNF-alpha, but not IL-1beta, inversely correlated with OC and NTx. These findings indicate that CINA patients have biochemical evidence of increased bone turnover which leads to decreased BMD. The elevated serum IL-1beta and TNF-alpha concentrations, suggestive of an underlying chronic inflammatory process in these patients, may be part of a mechanism accelerating bone turnover which, if prolonged, causes lowering of BMD.     

Serum osteocalcin concentrations in Paget's disease of bone

Total body scintiscans, serum alkaline phosphatase estimations, and serum osteocalcin radioimmunoassays were performed in 49 consecutive patients with Paget's disease of bone. Eleven were receiving calcitonin (salmon synthetic) at the time of the study. The serum alkaline phosphatase activities were elevated in all but one patient, with the highest value almost 50 times the upper limit of the reference range. Serum osteocalcin concentrations were elevated in 53% of patients and normal in the rest. The highest serum osteocalcin value was 4.2 times the upper limit of the reference range. The correlation coefficient between the extent of skeletal involvement and serum osteocalcin level was .70, while that between skeletal involvement and serum alkaline phosphatase level was .55. In spite of the better correlation between bone scintiscans and serum osteocalcin level, osteocalcin measurements are diagnostically less useful than serum alkaline phosphatase estimations in patients with Paget's disease of bone.     

Decreased bone area, bone mineral content, formative markers, and increased bone resorptive markers in endogenous Cushing's syndrome.

It is well established that chronic excess of glucocorticoids has negative effects on bone and collagen turnover, and that secondary osteoporosis is a known clinical complication of endogenous Cushing's syndrome (CS). The aim of the present study was to evaluate bone dimension and bone mineral content in relation to biochemical markers of bone and collagen turnover, in a consecutive series of 23 patients with endogenous CS (18 with pituitary adenoma and 5 with adrenal tumor; 17 women, 6 men; mean age 39.7+/-2.8 (S.E. M.) and 44.3+/-3.1 years respectively), compared with 23 age-, sex- and body mass index-matched healthy controls. Bone mineral densities were uniformly reduced in the different regions analyzed: lumbar spine (16.1%, P<0.001), femoral neck (15.2%, P<0.001), total body (11.5%, P<0.001), and the subregions of arms (8.4%, P<0.05), legs (10.1%, P<0.05) and trunk (15.8%, P<0.001). Similar results were observed for bone mineral content, although these were less prominent. The calculated area was significantly decreased in trunk (13.8%, P<0.01) and total body (11.6%, P<0.05). Serum levels of osteocalcin were significantly decreased (28%, P<0.03) in patients with CS. No significant differences were observed for the formative markers carboxyterminal propeptide of type I procollagen and aminoterminal propeptide of type I procollagen. Markers of bone resorption, serum Crosslaps and carboxyterminal cross-linked telopeptide of type I collagen were increased in patients compared with controls, although only significantly for Crosslaps (P<0.02). No correlations between formative and resorptive markers were found in the patients, but in controls, the formative markers were positively correlated with resorptive markers. In conclusion, bone dimension and bone mineral content of the entire skeleton are found to be decreased in endogenous CS. As judged by biochemical markers of bone remodeling, this is caused by decreased bone formation and an increased bone resorption.     

High prevalence of morphometric vertebral deformities in patients with inflammatory bowel disease

BACKGROUND: Earlier studies have documented that the prevalence of decreased bone mineral density (BMD) is elevated in patients with inflammatory bowel disease. The objective of this study was to investigate the prevalence of vertebral deformities in inflammatory bowel disease patients and their relation with BMD and bone turnover. METHODS: One hundred and nine patients with Crohn's disease (CD) and 72 with ulcerative colitis (UC) (age 44.5+/-14.2 years) were studied. BMD of the hip (by dual X-ray absorptiometry) was measured and a lateral single energy densitometry of the spine for assessment of vertebral deformities was performed. Serum markers of bone resorption (carboxy-terminal cross-linked telopeptide of type I collagen) and formation (procollagen type I amino-terminal propeptide) were measured, and determinants of prevalent vertebral deformities were assessed using logistic regression analysis. RESULTS: Vertebral deformities were found in 25% of both CD and UC patients. Comparing patients with and without vertebral deformities, no significant difference was found between Z-scores and T-scores of BMD, or levels of serum carboxy-terminal cross-linked telopeptide of type I collagen and serum procollagen type I amino-terminal propeptide. Using logistic regression analysis the only determinant of any morphometric vertebral deformity was sex. The presence of multiple vertebral deformities was associated with older age and glucocorticoid use. CONCLUSION: The prevalence of morphometric vertebral deformities is high in CD and UC. Male sex, but neither disease activity, bone turnover markers, clinical risk factors, nor BMD predicted their presence. The determinants for having more than one vertebral deformity were age and glucocorticoid use. This implies that in addition to screening for low BMD, morphometric assessment of vertebral deformities is warranted in CD and UC.     

Association between serum leptin concentrations and bone mineral density, and biochemical markers of bone turnover in adult men.

Leptin, the product of the ob gene, has been shown to inhibit bone formation in mice. We addressed whether leptin has any role in the regulation of bone mineral density (BMD) in humans. Subjects were 221 adult men with a mean (+/-SD) age and body mass index of 52.1 +/- 8.7 yr and 23.6 +/- 2.8 kg/m2. Serum leptin, carboxyterminal propeptide of type 1 procollagen (PICP; a marker of bone formation), and cross-linked carboxyterminal teleopeptide of type 1 collagen (a marker of bone resorption) were measured by RIA. BMD was assessed by single photon absorptiometry, and total fat mass was determined by bioimpedance analysis. BMD was inversely associated with serum leptin concentrations and total fat mass after adjustment for body weight. PICP, but not cross-linked carboxyterminal teleopeptide of type 1 collagen, was inversely correlated with serum leptin. These results may suggest that an increase in serum leptin reduces bone formation and decreases BMD in adult men. Leptin may be a regulator of BMD in humans.     

Effects of a growth hormone receptor antagonist on bone markers in acromegaly

OBJECTIVE: Excess GH secretion, as occurs in acromegaly, is associated with abnormalities in bone turnover markers and bone mineral density (BMD). GH administration in GH deficient patients causes an increase in bone turnover. IGF-I mediates many of the metabolic actions of GH, although GH may have direct effects upon bone. In patients with acromegaly who are treated with a GH receptor antagonist, selective blockade of the GH receptor results in a decrease in circulating IGF-I levels in the majority of cases. We hypothesized that, in acromegaly, antagonism of GH receptors would result in a decrease in serum markers of bone turnover, including serum procollagen I carboxy-terminal propeptide (PICP), osteocalcin and N-telopeptide (NTx). DESIGN AND SUBJECTS: Twenty-seven patients with acromegaly were enrolled as part of a multicentre 12-week trial of a GH receptor antagonist and were randomized to placebo (n = 7) or 10, 15 or 20 mg of pegvisomant (n = 20). MEASUREMENTS: Serum markers of bone turnover were determined at baseline and 12 weeks. RESULTS: Baseline bone turnover markers were above the upper limit of normal in 23%, 19% and 32% of subjects for osteocalcin, PICP and NTx, respectively. During the 12-week placebo-controlled period, there were significant decreases in serum markers of bone formation, osteocalcin (-2.2 +/- 0.44 vs. placebo +0.01 +/- 0.39 nmol/l, P = 0.009) and PICP (-23.6 +/- 9.6 vs. placebo +18.1 +/- 12.8 micro g/l, P = 0.022) and a serum marker of bone resorption, NTx (-4.4 +/- 1.4, placebo +1.0 +/- 0.3 nm, P = 0.024). CONCLUSIONS: Using a specific GH receptor antagonist, we found that normalization of IGF-I is associated with rapid reductions in markers of both bone formation and resorption, and that these processes remain coupled. These data confirm the highly significant effects of GH and IGF-I in modulating bone turnover. The independent contributions of GH and IGF-I to these effects and the long-term effects on BMD in this population remain to be determined.     

Bone mineral metabolism in adults with beta-thalassaemia major and intermedia

Bone disease is an important cause of morbidity in older patients with beta-thalassaemia major and intermedia. We studied 27 women and 23 men with beta-thalassaemia major (37) and intermedia (13) whose mean age was 32.3 +/- 9.7 years. Bone mineral density (BMD) of the lumbar spine, femoral neck and distal radius was determined by dual-energy X-ray absorbiometry (DXA). The longitudinal change in BMD over a mean of 5.6 years was determined in 19 patients. Serum 25-hydroxyvitamin D, insulin growth factor-1 (IGF-1), bone formation markers bone-alkaline phosphatase, osteocalcin and the resorption marker urinary N-telopeptide cross-linked type 1 collagen (NTx) were determined. The BsmI vitamin D receptor (VDR) gene polymorphism was analysed. Reduced BMD (Z-score < -2) was present in 89%, 62% and 73% of patients in the spine, hip and radius respectively. Vitamin D deficiency was found in 62%, decreased IGF-1 in 72% and increased urinary NTx in 84% of patients. Serum IGF-1 correlated with spine and hip BMD (r = 0.4, r = 0.39, P < 0.01 respectively), and NTx correlated with the hip BMD Z-score (r = 0.35 P < 0.05). The mean annual percentage change in spine BMD was -1.36%. Patients with the VDR BB genotype had lower spine BMD than patients with the bb genotype. In conclusion, bone loss continues in adult thalassaemia patients and is associated with increased bone resorption and decreased IGF-1. The BsmI VDR gene polymorphism is associated with osteopenia in thalassaemia.     

Relationship between biochemical markers of bone turnover and bone scintigraphic indices in assessment of Paget's disease activity

Objective. To evaluate the relationship between biochemical markers of bone turnover and bone scan indices of disease activity, as well as to analyze their variations based on skeletal involvement, in Paget's disease. Methods. Serum samples were obtained from 51 patients with Paget's disease to determine the levels of total alkaline phosphatase (total AP), bone alkaline phosphatase (bone AP), propeptide carboxyterminal of type I procollagen (PICP), propeptide aminoterminal of type I procollagen (PINP), osteocalcin, tartrate-resistant acid phosphatase, and telopeptide carboxyterminal of type I collagen. Urine samples were analyzed for levels of hydroxyproline (HYP), pyridinoline (PYR), deoxypyridinoline (DPYR), C-terminal telopeptide of type I collagen (CTx), and N-terminal telopeptide of type I collagen (NTx). In addition, 2 semiquantitative scintigraphic indices, disease activity (AI) and disease extent (EI), were obtained. Pagetic skeletal locations were evaluated individually, with special attention to skull involvement. Results. All biochemical markers correlated with the AI and the EI. Serum PINP, bone AP, and total AP showed the highest proportions of increased values among the bone formation markers (94%, 82%, and 76%, respectively). Among the bone resorption markers, urinary NTx showed the highest proportion of increased values in patients with Paget's disease (96%), compared with PYR (69%), DPYR (71%), CTx (65%), and HYP (64%). In patients with mild disease activity, serum PINP was the marker with the highest proportion of increased values (71%). In contrast, serum PICP and urinary CTx were the most discriminative markers for skull involvement. Except for higher values for most of the biochemical markers of bone turnover in flat bones, no major differences in other skeletal locations were observed. Conclusion. The determination of serum PINP as a marker of bone formation and urinary NTx as a marker of bone resorption provided the best biochemical profile to ascertain the extent and activity of Paget's disease. In patients with skull involvement, serum PICP and urinary CTx were shown to be the most discriminative markers.     

Serum osteocalcin in Paget's disease of bone: basal concentrations and response to bisphosphonate treatment

Serum osteocalcin concentrations were measured in 42 patients with Paget's disease of bone and elevated serum alkaline phosphatase (AP) levels. High serum osteocalcin levels were found in only 22 patients. Serum osteocalcin was significantly correlated with urinary hydroxyproline excretion (r = 0.747; P less than 0.001) and, to a lesser extent, with serum AP levels (r = 0.483; P less than 0.01). In 23 patients who were followed during treatment with iv (3-amino-1-hydroxypropylidene) 1,1-bisphosphonate (APD) for 10 days, a dissociation among these 3 biochemical parameters was found. Urinary hydroxyproline excretion fell significantly (P less than 0.001), serum AP levels decreased, but not significantly, and serum osteocalcin concentrations increased progressively (P less than 0.001). This increase was greater when initial levels were lower than expected for the activity of the disease. The rise in serum osteocalcin correlated significantly with the concomitant increase in serum 1,25-dihydroxyvitamin D concentrations. Three months after initiation of treatment, all 3 parameters, urinary OHP excretion, serum AP, and serum osteocalcin levels, were near or within the normal range. These results indicate that serum osteocalcin is not a clinically useful parameter for assessment of the activity of Paget's disease. Its basal concentrations lag behind those expected from the activity of the disease, suggesting defective osteocalcin production. It appears that the functions of osteocalcin and AP as well as their initial expression by the osteoblasts are different and that this difference may be important for the quality of bone formed in Paget's disease. APD can modulate the release of osteocalcin, possibly through stimulation of 1,25-dihydroxyvitamin D production, although other factors may be involved.     

Serum markers of bone metabolism in multiple myeloma: prognostic value of the carboxy-terminal telopeptide of type I collagen (ICTP)

This study was performed to evaluate the prognostic significance of serum markers of bone and collagen metabolism in multiple myeloma. Serum C-terminal telopeptide of type I collagen (ICTP) reflects degradation of bone, whereas serum osteocalcin, together with serum C-terminal propeptide of procollagen type I (PICP) and serum bone-specific alkaline phosphatase (bAP) reflect synthesis of bone matrix. The N-terminal propeptide of procollagen type III (PIIINP) in serum reflects synthesis of type III collagen. We analysed frozen sera from 109 patients with newly diagnosed multiple myeloma. Serum ICTP was elevated (>5.0μg/l) in most patients (median 6.6 μg/l, range 1.4–29.4 μg/l). Serum PIIINP was elevated (>4.2μg/l) in 46% (median 4.0 μg/l, range 1.4–20.1 μg/l). Serum PICP was generally within the reference limits, whereas serum osteocalcin and serum bAP were elevated in 19% and 37%, respectively. Serum ICTP correlated with serum PIIINP, serum β₂-microglobulin (β₂m), serum calcium, performance status, and stage. In univariate analysis, the test variables serum ICTP ( P =0.026) and serum osteocalcin ( P =0.036) were found to be of prognostic value, but PIIINP, PICP, or bAP in serum were not. Serum ICTP and serum β₂m had a similar prognostic value. In multivariate analysis, serum calcium showed the highest prognostic significance, and serum β₂m was the only other variable of independent prognostic value. However, in normocalcaemic patients, serum ICTP showed the highest prognostic significance, followed by serum osteocalcin. Thus, the serum levels of ICTP and osteocalcin seem related to bone turnover and calcium metabolism, and provide further information about myeloma activity, particularly in normocalcaemic patients.     

Increased urinary N-telopeptide cross-linked type 1 collagen predicts bone loss in patients with inflammatory bowel disease

OBJECTIVE: Reduced bone mineral density (BMD) is common in patients with inflammatory bowel disease (IBD), but the factors associated with its longitudinal rate of change have not been established. We prospectively assessed the rate of change in BMD, and its association with biochemical markers of bone turnover. METHODS: Twenty-two patients with Crohn's disease and 14 ulcerative colitis patients age 37.1 +/- 11.6 yr were followed for 2 yr. Lumbar spine (L2-L4) and femoral neck BMD were measured by dual x-ray absorptiometry at baseline and 24 months. Bone-specific alkaline phosphatase, osteocalcin, urinary N-telopeptide crosslinked type 1 collagen (NTx), parathyroid hormone, and 25-hydroxyvitamin-D were determined at baseline. RESULTS: At baseline, 59% of Crohn's patients and 43% of ulcerative colitis patients were osteoporotic, with spine or femoral neck BMD T-score < -2.5. Spine BMD, and spine and femoral neck T-scores were lower and disease duration was longer in nine patients with ileal resection compared with nonoperated patients (0.84 +/- 0.15 g/cm2 vs 0.96 +/- 0.11 g/cm2, -3.0 +/- 1.5 vs -1.7 +/- 1.3, -3.2 +/- 1.5 vs -2.2 +/- 1.0, respectively; all p < 0.05). At 24 months, 13/36 (36%) and 14/36 (39%) patients experienced spinal and femoral neck bone loss, respectively, with mean annual percent BMD changes of -2.0% and -1.5%, respectively. NTx, a bone resorption marker, inversely correlated with spinal BMD rate of change (r = -0.4, p < 0.05). Using quartiles analysis, patients with the highest NTx (Q4) experienced the greatest decrease in spine BMD compared with patients with the lowest NTx (Q1). CONCLUSIONS: Spine and femoral neck bone loss continues over time in more than one-third of IBD patients. Increased NTx level predicts spinal bone loss in IBD patients.     

Abnormal bone turnover in monoclonal gammopathy of undetermined significance: analyses of type I collagen telopeptide,osteocalcin, bone-specific alkaline phosphatase and propeptides of type I and type III procollagens

Abstract: The main difference between monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) is the presence of lytic bone destructions in the latter. About 20% of MGUS patients develop MM, and histomorphometric studies have shown disturbed bone turnover rates in some of these patients. This study was performed in order to evaluate whether serum analyses of the C-terminal telopeptide of type I collagen (ICTP), as a reflector of bone degradation, and of osteocalcin, bone-specific alkaline phosphatase (bAP) and the C-terminal propeptide of type I procollagen (PICP), as markers of bone formation, might give information on disturbancies of bone metabolism in MGUS. Furthermore, serum N-terminal propeptide of procollagen III (PIIINP) might give information on disturbances in collagen III metabolism in the bone marrow. In the 35 patients examined, serum ICTP was elevated in 12 patients (34%), serum PIIINP elevated in 6 patients (17%), serum osteocalcin elevated in 11 patients (31%), serum bAP elevated in 6 patients (17%), and serum PICP elevated in 4 patients (11%). Serum ICTP correlated significantly with PIIINP (r=0.72, p<0.001), and with serum osteocalcin (r=0.57, p<0.001) and serum bAP (r=0.51, p=0.002). These findings indicate disturbancies of bone turnover and affected collagen metabolism in some MGUS patients. Follow-up observation may reveal any prognostic value of these findings.