Characteristics of biochemical markers for bone formation in the elderly

Currently, several promising biochemical markers for bone metabolism have been postulated and expected to be applied to their clinical use. Among these markers, circulating levels of bone Gla-protein (BGP) and carboxyterminal peptide of type I procollagen (P1CP) have been established as non-invasive indices to assess bone turnover, especially bone formation. We investigated age-related effects on serum levels of both peptides and relationships between loss of bone mass and biochemical indices in the elderly. Fasting blood sample were obtained from 330 healthy volunteers to simultaneously measure serum BGP, serum P1CP and serum tartrate-resistant acid phosphatase (TRACP) as a marker for bone resorption. Serum BGP levels were found almost stable throughout life in men with a tendency to decrease in the elderly. Serum P1CP levels linearly decreased towards 50 to 60 years of age in men, followed by its constant increase with aging afterwards. Although a constant increase in serum P1CP levels were noted in women with aging, serum BGP levels were found remarkably elevated during menopausal periods of 50 to 70 years of age, followed by its wide distribution in the elderly. Both serum BGP and P1CP levels were elevated accompanied with age-related decrease in glomerular filtration rates in the elderly. In addition, a bone specific index, TRACP/BGP ratio consolidated the negative correlation between serum TRACP and % changes of bone mineral density (BMD). However, TRACP/P1CP ratio had nothing to do with % change of BMD. In conclusion, loss of bone mass could be predicted by bone specific indices, particularly in elderly women with widely distributed bone turnover. The data in this paper were reported in part in International Coference on Osteoporosis, Kobe, November 1991.     

Biochemical Markers of Bone Turnover in Men

Although osteoporosis in men has been recently recognized as a public health problem, the mechanisms leading to bone loss are still poorly understood. Longitudinal studies of bone mineral density suggest an acceleration of bone loss after 70 years of age. Histomorphometric data concerning age-related changes of bone turnover in men are limited, including few men over 70 years and have been restricted to the trabecular envelope of bone biopsies. Most measurements of biochemical markers of bone turnover have been performed in small cohorts of limited age range, and results obtained in large cohorts are scanty. Levels of markers of bone formation and of bone resorption are very high in men aged 20-30 years which corresponds to the late phase of formation of peak bone mass, and then declines, reaching their lowest levels between 50 and 60 years. Data on bone turnover markers in elderly men are discordant. Concentrations of bone formation markers remain stable, decrease slightly, or even increase marginally. Markers of bone resorption increase in some studies, mainly after 70 years of age, in line with acceleration of bone loss in this age range. This discordance between studies can result from different reasons. The increase of bone turnover may be limited to a subgroup of elderly men. In addition, urinary levels of bone resorption markers depend on the rate of bone turnover, on pre-renal and renal catabolism of peptides released from bone matrix, on glomerular filtration rate, as well as unit of expression of their results (per 24 hours per urinary creatinine mass, per glomerular filtrate volume). In elderly men, biochemical bone markers are negatively correlated with bone mineral density. Longitudinal studies are not yet available on the relationship among bone turnover markers, rate of bone loss, and fracture. In conclusion, in elderly men, age-related bone loss seems to result from increased bone resorption which is not matched by increased bone formation. Thus, antiresorptive therapy may be of interest in the prevention and treatment of osteoporosis in men. Further studies are necessary to determine if bone resorption markers predict the risk of fragility fractures in elderly men.     

Inverse association between bone turnover rate and bone mineral density in community-dwelling men >70 years of age: no major role of sex steroid status

Bone loss is accelerated in elderly men. Little is known about the pathophysiology of senile bone loss or about the role played by relative sex steroid deficiency in the determination of bone turnover in elderly men. In a population-based sample of 283 healthy, ambulatory men, aged 71-86 years, we sought to determine whether lower bone mineral density (BMD; using dual-energy X ray absorptiometry at the hip and the forearm) is associated with higher bone turnover, and we assessed the impact of sex steroid status on bone turnover. Indices of bone formation, serum osteocalcin (s-Oc), and bone-specific alkaline phosphatase (s-bAP) and indices of bone resorption, serum and urinary telopeptide of type I collagen (s-CTx and u-CTx), and urinary free deoxypyridinoline (u-Dpd) were intercorrelated (r = 0.29-0.76, p < 0.001). Bone turnover indices were negatively associated with BMD (r = -0.17 to -0.34, p < 0.01). In univariate analyses, there was a trend toward weak negative associations of bone turnover markers with serum free testosterone (FT), significant only for s-Oc and s-CTx (r = -0.16 and -0.14, p < 0.01), and with serum free estradiol (FE(2)), significant only for u-CTx and s-CTx (r = -0.18 and -0.19; p < 0.01). The lower quartile for FE(2) was associated with higher values of u-CTx (p = 0.003) and s-CTx (p < 0.001). However, in multivariate models, for the individual markers of bone turnover a negative association between estradiol (E(2)) or FE(2) and s-CTx was the only remaining (marginally) significant association (p < 0.05) for the relationship between sex steroids and any of the bone turnover indices assessed. In community-dwelling men age >70 years, bone turnover rate, as determined by biochemical markers, is a significant negative determinant of prevalent BMD. However, the findings do not support the view that relative differences in sex steroid status, as observed among healthy elderly men, have a major impact on bone turnover.     

Role of Vitamin D and Parathyroid Hormone in the Regulation of Bone Turnover and Bone Mass in Men: The MINOS Study

We investigated the role of vitamin D and of parathyroid hormone (PTH) in the regulation of bone mineral density (BMD), tone dimensions and seasonal variation of bone turnover in 881 men aged 19–85 years. Bone mineral content (BMC) and BMD of the lumbar spine, hip and whole body were measured with HOLOGIC 1000W and those of distal forearm with an OSTEOMETER DTX 100 device. Bone formation was evaluated using osteocalcin, bone alkaline phosphatase and N-terminal extension propeptide of type I collagen (PINP). Bone resorption was evaluated by 24-hour excretion of deoxypyridinoline and of C-terminal telopeptide of collagen type I. In young men (<55 yrs) PTH level decreased with age (r = –0.18, P < 0.005) whereas 25-hydroxyvitamin D (25OHD) concentration was stable. In older men (>55 years) 25OHD decreased whereas PTH increased with age (r = –0.27 and r = 0.21, P = 0.0001). In young men, 25OHD level varied with season but not PTH, biochemical markers of bone turnover nor BMD. In young men, 25OHD, but not PTH, was a significant determinant of BMC, cortical thickness and of biomechanical properties of the femoral neck. Biochemical bone markers and BMD were not correlated with PTH nor with 25OHD. In elderly men, winter levels of 25OHD were lowest whereas those of PTH, bone resorption markers and PINP were highest. After adjustment for age, body weight and season, biochemical markers of bone turnover were correlated with PTH. In elderly men, 25OHD and PTH were significant determinants of BMC, cortical thickness and of biomechanical parameters of the femoral neck. Men with vertebral deformities had lower concentrations of 25OHD, higher PTH levels and slightly elevated urinary excretion of biochemical markers of bone resorption compared with men without vertebral deformities. In conclusion, in young men, 25OHD discloses a seasonal variability in contrast to PTH and biochemical bone markers. In this group, 25OHD is a significant determinant of BMC and BMD but not of bone size. In elderly men, seasonal variation of 25OHD and PTH concentrations result in seasonal variation of bone resorption. In this group, both 25OHD and PTH are determinants of BMC and cortical thickness of the femoral neck and, consequently, of its mechanical parameters.     

Bone resorption and osteoporotic fractures in elderly men: the dubbo osteoporosis epidemiology study.

Among the potential risk factors for fragility fractures, bone turnover is considered an important determinant. In a case-cohort control study of 151 elderly men followed prospectively over 6.3 years, high bone resorption as assessed by S-ICTP was associated with increased risk of osteoporotic fracture, independent of BMD. Combining measurements of BMD and bone turnover may improve fracture prediction in elderly men. INTRODUCTION: Approximately one-third of osteoporotic fractures occur in men. Among the potential risk factors for fragility fractures, bone turnover is considered an important determinant. The association between fracture risk and rates of bone turnover has not been well established in men. We examined this relationship in elderly community-dwelling men. MATERIALS AND METHODS: This case-cohort control study included 50 men with incident low-trauma fractures (cases; age, 72.3 +/- 6.7 years) and 101 men without fracture (controls; age, 70.4 +/- 4.1 years), who have been prospectively followed in the Dubbo Osteoporosis Epidemiology Study for a median of 6.3 years (range, 2-13 years). BMD at the lumbar spine (LSBMD) and at the femoral neck (FNBMD) and markers of bone turnover were measured at baseline. Bone resorption was assessed by measuring nonfasting serum concentrations of the carboxyterminal cross-linked telopeptide of type I collagen (S-ICTP) and of a linear octapeptide derived from the carboxyterminal type I collagen telopeptide (S-CTX). Bone formation was assessed by measuring the serum levels of the aminoterminal propeptide of type I procollagen (S-PINP). RESULTS: Men with subsequent fractures had lower BMD at baseline, both at the femoral neck and the spine, lower dietary calcium intake, and higher S-ICTP levels than age-and weight-matched controls. Smoking habits, S-CTX, and S-PINP did not differ between groups. Based on univariate regression analyses, S-ICTP (relative risk [RR] for 1 SD change: 1.8; 95% CI, 1.4-2.3) and serum creatinine levels (RR, 1.4; 95% CI, 1.1-1.7) were associated with increased risk of fracture. In multivariate regression analyses, S-ICTP (RR, 1.4; 95% CI, 1.0-1.9) and FNBMD (RR, 1.8; 95% CI, 1.4-2.3) remained independent predictors of fracture risk. Men within the highest quartile of S-ICTP had a 2.8-fold (95% CI 1.4-5.4) increased risk of fracture compared with those in the lowest quartile. The incidence of osteoporotic fractures was 10 times higher in men with high S-ICTP and low FNBMD compared with men with low S-ICTP and high FNBMD. Of the fracture risk in the population, 20% was attributable to high S-ICTP and low FNBMD, and S-ICTP contributed 17% to this increased risk. CONCLUSION: High bone resorption is associated with an increased risk of osteoporotic fracture in elderly men, independent of BMD. Combining measurements of BMD and bone turnover, which correlated with fracture in this cohort, could improve fracture risk prediction in elderly men.     

Increased Bone Resorption Is Associated With Higher Mortality in Community‐Dwelling Men ≥50 Years of Age: The MINOS Study

Low BMD, high concentration of 17β‐estradiol (17βE2), and decreased level of 25‐droxycholecalciferol [25(OH)D] predict mortality. Our hypothesis is that high levels of biochemical bone turnover markers (BTMs) are independent predictors of mortality in home‐dwelling men. In 781 men ≥50 yr of age followed up prospectively for 10 yr, we studied the association of BTMs with mortality after adjustment for confounders including BMD, major osteoporotic fractures, and concentrations of 17βE2 and 25(OH)D. Men who died had lower BMD and higher BTM levels. In multivariate models, mortality was higher in men with low BMD (lowest quartile) at the total hip, whole body, and ultradistal radius (HR = 1.49–1.70, p < 0.05). After exclusion of the first 3 yr, higher levels (fourth quartile) of bone resorption markers (free and total deoxypyridinoline and urinary and serum type I collagen C‐telopeptide) predicted mortality in multivariate models adjusted for age, BMI, smoking habits, alcohol intake, physical performance and activity, comorbidities, total hip BMD, major osteoporotic fractures, creatinine clearance, season, and concentrations of 17βE2 and 25(OH)D (HR = 1.58–2.44, p < 0.05–0.001). In conclusion, in older community‐dwelling men, increased bone resorption markers levels predicted mortality regardless of age and other confounders. Thus, in older men, high bone resorption may reflect poor current health status and poor aging.     

Sexual differences in bone markers and bone mineral density of normal Chinese

We measured bone mineral density (BMD) at lumbar (L2–L4) vertebrae and proximal femurs of 385 healthy Chinese women aged 40–70 years and 156 healthy Chinese men aged 20–85, and four markers—bone alkaline phosphatase isozyme (BAP), procollagen-I C terminal propeptide (PICP), osteocalcin (BGP) in serum, and a bone resorption marker, urinary cross-linked N-telopeptide of type I collagen (NTX), of these subjects. The results indicate that in postmenopausal women, levels of all the markers increased with age. In men, serum BAP, PICP, and urinary NTX decreased significantly, and serum BGP decreased with borderline significance (P=0.08). With increasing age, bone density decreased at both sites in post-menopausal women and at the proximal femur in men. The lumbar bone density showed no significant age-related changes in men. In premenopausal women, BMD at either site showed no significant change with increasing age. Despite the different trends between men and women of agerelated changes in BMD and bone markers, bone density of both proximal femur and spine in both sexes correlated inversely with levels of the bone markers in a manner independent of age or body weight. The meaning of opposite age effects on bone markers in men and women needs further investigation. In addition, higher bone marker levels, implying faster bone turnover rate, are associated with lower BMD in both sexes.     

Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: the OFELY study.

The mechanisms leading to increased bone loss and skeletal fragility in women with postmenopausal osteoporosis are still poorly understood. Increased bone resorption, low serum estradiol and high serum sex-hormone-binding globulin (SHBG) recently have been reported as predictors of vertebral and hip fractures in elderly women. In a cohort of healthy untreated younger postmenopausal women aged 50-89 years (mean, 64 years), we compared baseline levels of bone markers and endogenous hormones in 55 women who subsequently had a fracture (20 vertebral and 35 peripheral fractures) with levels in the 380 women who did not fracture during a mean 5 years of follow-up. Women with levels in the highest quartile of four bone resorption markers including urinary-free deoxypyridinoline (D-Pyr), urinary type I collagen N-telopeptides (NTX), and urinary and serum type I collagen C-telopeptides (CTX) had about a 2-fold increased risk of fractures compared with women with levels in the three lowest quartiles with relative risk (RR) and 95% CI of 1.8 (1.0-3.4) for free D-Pyr, 1.7 (0.9-3.2) for urinary NTX, 2.3 (1.3-4.1) for urinary CTX, and 2.1 (1.2-3.8) for serum CTX. Serum levels of bone alkaline phosphatase (BAP) in the highest quartile were associated with an RR of fracture of 2.4 (1.3-4.2). Women with serum levels of estradiol and dehydroepiandrosterone (DHEA) sulfate in the lowest quartile had an RR of fracture of 2.2 (1.2-4.0) and 2.1 (1.2-3.8), respectively. Increased levels of SHBG and intact parathyroid hormone (PTH) were moderately associated with an increased risk of fracture. Similar results were obtained when the analysis was restricted to symptomatic vertebral and nonvertebral fractures. Adjustment of biochemical markers by hormone levels did not significantly alter the results. Women with both high bone resorption markers and low estradiol (or low DHEA sulfate) had a higher risk of fracture with RRs of 3.0-3.3 (p < 0.001). After adjustment for bone mineral density (BMD) of the hip, spine, radius, or total body, bone markers and hormones were still predictive of fracture risk with similar RRs. We conclude that high levels of some biochemical markers of bone turnover, low serum estradiol, low DHEA sulfate, high SHBG, and high PTH are associated with increased risk of osteoporotic fracture in postmenopausal women, independently of each other and of BMD. The mechanism by which some postmenopausal women have an increased rate of bone turnover leading to an increased risk of fracture remains to be elucidated.     

Biochemical markers of bone formation reflect endosteal bone loss in elderly men--MINOS study

In the skeleton of elderly men, two opposite activities occur: bone loss at the endosteal envelope, which increases bone fragility, and periosteal apposition, which improves bending strength of bone. Both may contribute to serum bone formation markers although they have an opposite effect on bone fragility. The aim of this study was to determine if circulating bone formation markers reflect periosteal bone formation and endosteal bone remodelling in 640 men aged 55-85 years belonging to the MINOS cohort. We measured biochemical markers of bone formation (osteocalcin, bone alkaline phosphatase, N-terminal extension propeptide of type I collagen) and bone resorption (urinary and serum beta-isomerised C-terminal telopeptide of collagen type I, total and free deoxypyridinoline). Parameters of bone size (cross-sectional surface of third lumbar vertebral body measured by X-ray, projected areas of total hip, femoral neck, radius and ulna measured by dual-energy X-ray absorptiometry) increased with age (r = 0.20-0.32, P < 0.0001). In contrast, parameters related to bone loss (areal bone mineral density [aBMD], volumetric bone mineral density [vBMD] and cortical thickness) and determined mainly by bone resorption, decreased with ageing (r = -0.14 to -0.23, P < 0.005-0.0001). Men in the highest quartile of bone resorption markers had lower aBMD (3.8-10.2%, P < 0.05-0.0001), lower vBMD (3.9-13.0%, P < 0.05-0.0001), and lower cortical thickness (1.5-9.6%, P < 0.05-0.0001) than men in the lowest quartile. Markers of bone resorption were not significantly associated with estimates of bone size at any skeletal site. Markers of bone formation were not associated with estimates of periosteal formation after adjustment for covariates. In contrast, men in the highest quartile of the bone formation markers had significantly lower aBMD (4.0-11.7%, P < 0.05-0.0001), lower vBMD (4.2-16.3, P < 0.05-0.0001) and lower cortical thickness (4.0-7.4%, P < 0.05-0.0001) than men in the lowest quartile. In summary, serum levels of bone formation markers are negatively correlated with the estimates of endosteal bone loss. In contrast, they disclose no association with parameters reflecting periosteal apposition. Thus, in elderly men, bone formation markers reflect endosteal bone remodelling, probably because of the coupling between resorption and formation activities. In contrast, they do not reflect the periosteal bone formation, probably because the periosteal surface is smaller and has a slower remodelling rate than the endosteal surface.     

The relation between bone density, free androgen index, and estradiol in men 60 to 70 years old

The cause of age-related bone loss in men is poorly understood. Previous studies of the relationship between bone density and serum androgens have yielded inconsistent results, perhaps partly because age is a determinant of both. Recent studies suggest that serum estrogen levels influence bone density in adult men. In order to determine whether bone mineral density (BMD) and bone turnover are associated with serum sex steroids, we investigated 37 normal men within a narrow age range (60-70 years). Bone mineral density at the forearm, hip, and spine, testosterone, sex hormone binding globulin (SHBG), free androgen index (FAI:T/SHBG), estradiol (E), free estradiol index (FEI:E/SHBG), and markers of bone formation (alkaline phosphatase, osteocalcin, procollagen type I C-terminal extension peptide) and bone resorption (hydroxyproline/creatinine [OHPr/Cr], deoxypyridinoline/creatinine [Dpd/Cr], pyridinoline/creatinine, collagen type I cross-linked telopeptide) were measured. Bone mineral density was positively related (r > 0.35, p < 0.05 at all sites) to log FAI, whereas there was no significant relationship between BMD and either serum total testosterone, serum E, or FEI. Bone density at the spine and hip were inversely related to both OHPr/Cr (r > -0.41, p < 0.05 for all sites) and Dpd/Cr (r > -0.36, p < 0.05 for all sites). OHPr/Cr (r = -0.41, p < 0.05) and Dpd/Cr (r = -0.41, p < 0.05) were both inversely related to log FAI. We conclude that BMD and bone turnover in adult men are related to plasma free androgens.     

Role of parathyroid hormone in mediating age-related changes in bone resorption in men

Osteoporosis in men is an important and growing public health problem. While there has been extensive work done on defining the mechanism(s) of the age-related increase in bone resorption in women, our knowledge regarding the pathogenesis of bone loss in elderly men is still incomplete. We previously demonstrated that the age-related increase in serum PTH contributes substantially to the increased bone resorption in elderly women, since suppression of PTH levels by an intravenous calcium infusion decreased bone resorption markers to a greater extent in elderly compared to premenopausal women. In the present study, we tested the hypothesis that the comparable increase in PTH levels in elderly men (age 70–78 years) was driving bone resorption to a greater extent in these men than in younger men (age 40–50 years). PTH secretion was suppressed by an intravenous calcium infusion and the corresponding changes in the bone resorption marker, urine N-telopeptide of type I collagen (NTx) were assessed. In contrast to our previous findings in pre- versus postmenopausal women, suppression of PTH secretion in elderly men did not result in a greater decrease in urine NTx excretion than in the younger men (change in NTx excretion in the elderly men, -2.79±1.99 nmol/mmol Cr, versus that in the younger men, –5.07±1.39 nmol/mmol Cr, P=0.356). Collectively, these data suggest that the relationship between the age-related increase in serum PTH levels and bone resorption differs between elderly men and women. Since both estrogen and testosterone can attenuate the bone resorbing effects of PTH, it is possible that this difference may be due to the much milder degree of sex steroid deficiency in elderly men as compared to postmenopausal women.     

Biochemical Markers of Bone Turnover Reflect Femoral Bone Loss in Elderly Women

Although over 90% of hip fractures occur in patients over age 70, few data are available on femoral bone loss in this age group. To examine the relationship between biochemical markers of bone turnover and femoral bone loss in the elderly, 36 female and 17 male, healthy, community-dwelling elderly over age 65 (mean ± SD age: women 71 ± 4 years, men 75 ± 5 years) were followed for 3 years. Annual bone mineral density measurements of the hip and lumbar spine by dual-energy x-ray absorptiometry (DXA) were obtained and biochemical markers of bone resorption (urinary N-telopeptide crosslinks, free pyridinoline, total pyridinoline, total deoxypyridinoline, and hydroxyproline) and bone formation (serum osteocalcin, bone-specific alkaline phosphatase) were obtained at the end of year 3. In elderly women, longitudinal bone loss at the total hip was negatively correlated with markers of bone resorption (r =−0.39 to −0.52, P < 0.05), bone formation (r =−0.38, P < 0.05), and age (r =−0.39, P < 0.05). Markers of bone resorption were correlated with markers of bone formation (r = 0.63 to 0.74, P < 0.01). In multiple regression analysis, urinary N-telopeptide crosslinks (marker of resorption), serum osteocalcin (marker of formation), and serum parathyroid hormone explained 43% of the variability of bone loss at the total hip in women. These parameters were not related to bone loss in men. We conclude that femoral bone loss increases with age in women over 65. Measurements of specific biochemical markers of bone turnover are correlated with longitudinal bone loss in elderly women. These markers may help identify women at greatest risk for bone loss who would benefit most from therapeutic interventions. Received: 28 January 1996 / Accepted: 3 May 1996     

Association between bone turnover rate and bone microarchitecture in men: The STRAMBO study

Few data concern the relationship between bone turnover and microarchitecture in men. We investigated the association between levels of biochemical markers of bone turnover (BTM) and bone microarchitecture in 1149 men aged 19 to 85 years. Bone microarchitecture was assessed by high‐resolution peripheral quantitative computed tomography at the distal radius and tibia. Bone formation was assessed by serum osteocalcin, bone alkaline phosphatase, and N‐terminal extension propeptide of type I collagen. Bone resorption was assessed by serum C‐terminal telopeptide of type I collagen and urinary excretion of total deoxypyridinoline. BTM levels were high in young men and decreased until age 50 years. Urinary deoxypyridinoline (DPD) increased after age 70 years, whereas other BTMs remained stable. Before 50 years of age, only cortical volumetric bone mineral density (D_cort) correlated negatively with BTM levels. Between 50 and 70 years of age, D_cort and some microarchitectural parameters correlated significantly with BTM at the radius and tibia. After 70 years of age, higher BTM levels were associated with lower cortical thickness and D_cort at both the skeletal sites. At the distal radius, men in the highest BTM quartile had lower trabecular density, number (Tb.N), and thickness (Tb.Th) and more heterogeneous trabecular distribution compared with men in the lower quartiles. At the distal tibia, higher BTM levels were associated with lower Tb.N and Tb.Th in the central but not subendocortical area. Thus, in men, bone microarchitecture depends weakly on the current bone turnover rate until age 70. Thereafter, bone turnover seems to be a significant determinant of bone microarchitecture. © 2010 American Society for Bone and Mineral Research.     

Altered bone mineral metabolism in patients with osteoarthritis

OBJECTIVE: Investigation of the relationship between osteoarthritis (OA) and mineral density, and determination of any alteration in bone mineral, metabolism as assessed by biochemical markers of bone resorption and formation. METHODS: Forty females and 20 males were included in the study. Spinal OA as well as knee OA were defined from radiographs and graded according to Lane et al.'s and Spector et al.'s scoring systems. Bone mineral density (BMD) of the lumbar spine was measured by osteo CT. Bone turnover rates were estimated by measuring biochemical markers of bone resorption (urinary deoxypyridinoline) and bone formation (bone-specific alkaline phosphatase). Forty females and 20 males of the same age were studied as a control group. RESULTS: BMD was greater in women with spinal OA as compared to controls (P < 0.05). Also, males with OA had a non-significantly higher BMD than controls. The bone resorption markers were higher than normal values. However, they were lower than the control group. Similarly, the bone formation markers were lower as compared to the control group. CONCLUSION: Spinal OA is associated with higher BMD. This protective effect of spinal OA against osteoporosis may be mediated through decreased rate of bone turnover.     

老年2型糖尿病患者血尿酸水平与骨代谢、骨密度及骨质疏松的关系

目的探讨老年2型糖尿病患者血尿酸水平与骨代谢标志物、骨密度及骨质疏松的相关关系。方法选取2018-2019年于北京大学国际医院内分泌科门诊就诊及住院的年龄60岁以上的老年2型糖尿病患者,共计577人,其中男性289人,女性288人(均为绝经后女性)。对所有研究对象进行一般临床资料调查、生化指标及甲状旁腺素(PTH)、25羟维生素D[25(OH)D]、骨钙素(OC)、血清I型前胶原N-末端前肽(P1NP)、I型胶原交联C-末端肽(β-CTX)测定,计算估算肾小球滤过率(eGFR),双能X线吸收法(DXA)测定股骨颈(FN)及腰椎(L1~4)骨密度(bone mineral density,BMD)。将血尿酸(SUA)四分位法分层比较分析股骨颈及腰椎总BMD变化趋势,Pearson和Spearman相关分析SUA与血钙(Ca)、PTH及OC、P1NP、CTX、25(OH)D、腰椎及股骨颈BMD的关系,多因素Logistic回归分析SUA与骨质疏松的关系。结果SUA第4分组BMI、肌酐(Cr)、股骨颈及总腰椎BMD水平明显高于第1分位组,SUA第4分组eGFR水平明显低于第1分位组,差异具有统计学意义(P<0.05);Pearson相关分析显示SUA与股骨颈BMD(r=0.082,P=0.002)、糖尿病病程(r=0.129,P=0.005)、BMI(r=0.201,P=0.000)正相关,与eGFR负相关(r=-0.434,P=0.000),Spearman相关分析显示SUA与腰椎总BMD(r=0.168,P=0.003)、Ca(r=0.147,P=0.001)正相关,与β-CTX负相关(r=-0.157,P=0.001),与PTH、25(OH)D、OC、P1NP无相关性(P>0.05)。以老年2型糖尿病合并骨质疏松为因变量,多因素Logistic回归显示,调整年龄、eGFR、BMI、HbA1c后,SUA是老年2型糖尿病患者发生骨质疏松的保护因素(P=0.039,OR=0.452,95%CI:0.212~0.962)。结论在老年2型糖尿病患者中,正常偏高的血尿酸水平可能减少骨质疏松的发生风险。     

Anthropometrics and biochemical markers in men.

The relation between anthropometric components and biochemical markers has not been previously studied. To clarify the role of anthropometric factors in bone metabolism in men, 145 randomly selected subjects 40 to 70 yr of age from a population-based cohort were studied. Pearson's r and multiple regression analysis were used to assess the relation between anthropometrics (weight, body mass index [BMI], percentage of body fat, fat-free weight, and fat freeBMI), biochemical markers, and bone mineral density (BMD) at the spine and femoral neck, as well as between BMD and each biochemical marker (serum bone formation marker procollagen amino-terminal propeptide [PINP],urinary bone resorption marker amino-terminal telopeptide [NTx], and the ratio of PINP to NTx. Of the anthropometric factors, fat-free BMI had the highest association with the markers (r = -0.21 to -0.35, p < 0.05) and explained a higher percent of both spine BMD and NTx variance than weight. Body fat did not correlate with the BMD measures.Urinary NTx was a better indicator of current BMD status than PINP or the ratio of PINP to NTx, with the highest association with BMD at the sites tested (r = -0.20 to -0.29). NTx levels were statistically significantly different between men with normal and osteoporotic BMD at the femoral neck.     

Acute Effects of Calcitonin Nasal Spray on Serum C-telopeptide of Type 1 Collagen (CTx) Levels in Elderly Osteopenic Women with Increased Bone Turnover

Salmon calcitonin is a potent inhibitor of osteoclastic activity. The effect of calcitonin in elderly women with high bone turnover at higher risk of developing osteoporosis has not been studied. To investigate acute effects of calcitonin treatment on bone resorption markers in elderly women, we conducted a randomized trial in women >65 years of age with high bone turnover assessed as urinary N-telopeptide of type-I collagen (NTx) levels 1 SD higher than mean premenopausal levels, which was irrespective of bone density. A total of 98 elderly women were randomly assigned to receive either 200 IU calcitonin nasal spray (n = 75) with calcium (500 mg) and vitamin D (200 IU) or calcium and vitamin D (n = 23) alone for 6 months. Blood and urine samples were collected at 0, 2, 4, and 6 months and analyzed for urinary NTx and serum C-telopeptide of type-1 collagen (CTx). At baseline, mean age was 72.1 ± 4.7 (mean ± SD) in the calcitonin group and 72.2 ± 6 years in the control group. The spine and total hip BMD, serum PTH levels and urinary calcium/creatinine ratios were similar in both groups. Mean BMD was in the osteopenic range in both groups. Calcitonin treatment resulted in significant decreases in serum CTx levels, 2, 4 and 6 months after treatment as compared to baseline, and after 4 and 6 months as compared to controls. A maximum decrease from baseline of 33% was seen at 6 months. The urinary resorption marker, urine NTx, showed a significant decrease in the calcitonin group when compared to baseline only at the 6-month time point. Analysis of least significance change (LSC) showed that 70% of calcitonin patients were categorized as responders using serum CTx after 6 months of treatment. We conclude that 200 IU calcitonin effectively decreases bone resorption within 60 days of therapy, thus preventing further bone loss in elderly women who are at a high risk of developing osteoporosis.     

Biochemical markers of bone turnover after surgical menopause and hormone replacement therapy.

The objective of this study was to evaluate the effect of surgical menopause and hormone replacement therapy (HRT) on the new biochemical markers of bone turnover. Fourteen women who had undergone surgical menopause and began HRT 3 months after surgery were recruited for a 1-year study. Results were compared with a control group of 31 healthy premenopausal women of similar age. Serum samples were obtained to determine total alkaline phosphatase, bone alkaline phosphatase, propeptides carboxy- and amino-terminal of type I procollagen (PICP, PINP), osteocalcin, tartrate-resistant acid phosphatase, and carboxy-terminal telopeptides of type I collagen (ICTP and serum CTX). Urine samples were analyzed for hydroxyproline, pyridinoline, deoxypyridinoline, alpha- and beta-carboxy-terminal telopeptides of type I collagen (alpha-CTX and beta-CTX), and amino-terminal telopeptide of type I collagen (NTX). Determinations were performed after 3 months of surgical menopause and after 3 and 9 months of HRT. All biochemical markers increased after menopause, and most of them normalized after 9 months of HRT. Serum PINP showed the highest proportion of increased values after surgery among bone formation markers (62%), as well as the highest mean percent increase (101%). Among bone resorption markers in postmenopausal women, urinary beta-CTX, alpha-CTX, NTX, and serum CTX showed the highest proportion of increased values (100%, 67%, 58%, 58%, respectively) as well as the greatest mean percent increase. They were also the markers with the most marked response to HRT. In conclusion, serum PINP is the most sensitive marker of bone formation, whereas beta-CTX is the most sensitive marker of bone resorption after surgical menopause. In addition, both markers showed the highest response after HRT.     

Biochemical Markers of Bone Turnover and Bone Loss at the Lumbar Spine and Femoral Neck: The Taiji Study

The purpose of this study was to ascertain whether biochemical markers of bone turnover predict bone loss. The survey was carried out in Taiji, Wakayama Prefecture, Japan. From a list of inhabitants aged 40–79 years, 400 participants (50 men and 50 women in each of four age groups) were selected randomly. Bone mineral density (BMD) was measured, and blood and urine samples of all participants were examined to obtain values for eight biochemical markers: alkaline phosphatase (ALP), bone Gla protein (BGP), type I procollagen (carboxyterminal peptide of type I procollagen; PICP), cross-linked carboxyterminal telopeptide region of type I collagen (ICTP), and urinary excretion of calcium (Ca), phosphate (P), pyridinoline (Pyr), and deoxypyridinoline (D-Pyr). Each marker was evaluated as a predictor of the rate of bone change in lumbar spine and femoral neck BMD over a 3-year period. The value of Pyr was significantly related to the change of lumbar spine BMD in men (P= 0.009), and that of BGP was found to be significant in women (P= 0.045). By contrast, none of the bone markers significantly correlated with bone loss at the femoral neck. The coefficient of determination at the lumbar spine was 5% and 7% at the femoral neck only. We conclude that biochemical markers of bone turnover cannot predict bone loss rates in middle-aged or elderly Japanese men and women over a 3-year period with sufficient accuracy for use in clinical decision making. Received: 26 January 1998 / Accepted: 9 July 1998     

Biochemical assessment of bone turnover and bone fragility in men

SUMMARY: Osteoporosis in men is less studied than in women. Few data concern biochemical bone turnover markers (BTM) in men and their potential use. METHODOLOGY: We evaluated papers concerning BTM in men cited on Medline. Selection of studies were based on the number of subjects, age range, group homogeneity, follow-up duration, number of BTM. RESULTS: BTM levels are high in young men, then decrease with age.In elderly men, bone resorption increases with age more than bone formation. Variability of individual values is high and their significance is unclear. In elderly men, BTM levels correlate negatively with bone mineral density suggesting that accelerated bone turnover underlies age-related bone loss. Data on the prediction of accelerated bone loss and fractures by BTM in men are scant. Testosterone treatment induces a decrease in bone resorption followed by a decrease in bone formation. Bisphosphonates and calcitonin decrease BTM levels in osteoporotic men. Parathyroid hormone 1-34 and growth hormone induce a rapid increase in bone turnover followed by a progressive slowdown. CONCLUSIONS: Few studies concern BTM in men. Currently available data are not sufficient to suggest guidelines for the practical use of BTM in the clinical management of the osteoporosis in elderly men.