Lumbar spine peak bone mass and bone turnover in men and women: a longitudinal study

Summary  Peak bone mass is an important determinant of bone mass in later life, but the age of peak bone mass is still unclear. We found that bone size and density increase and bone turnover decreases until age 25. It may be possible to influence bone accrual into the third decade. Introduction  Peak bone mass is a major determinant of bone mass in later life. Bone growth and maturation is site-specific, and the age of peak bone mass is still unclear. It is important to know the age to which bone accrual continues so strategies to maximise bone mass can be targeted appropriately. This study aims to ascertain the age of lumbar spine peak bone mass. Methods  We measured lumbar spine BMC, estimated volume and BMAD by DXA and biochemical markers of bone turnover in 116 healthy males and females ages 11 to 40, followed up at an interval of five to nine years. Results  The majority of peak bone mass was attained by the mid-twenties. Increases in BMC in adolescents and young adults were mostly due to increases in bone size. Bone turnover markers decreased through adolescence and the third decade and the decreasing rate of change in bone turnover corresponded with the decreasing rate of change in lumbar spine measurements. Conclusions  Skeletal maturation and bone mineral accrual at the lumbar spine continues into the third decade.     

Can biochemical markers predict bone loss at the hip and spine?: A 4-year prospective study of 141 early postmenopausal women

A number of recent studies have suggested that non-invasive measures of bone turnover are associated with bone loss at the forearm in postmenopausal women. Whether bone turnover markers are predictive of bone loss from the clinically important sites of lumbar spine and femoral neck remain unclear, and was the aim of this 4-year prospective study. One hundred and forty-one normal, postmenopausal women (mean age 52.0±3.3 years, mean menopause duration 20.4±5.7 months) were recruited for the study in 1988. Fasting early morning samples of blood and urine were collected at the baseline visit and stored at –20 °C prior to analysis. Serum was assayed for osteocalcin, oestradiol, oestrone, oestrone sulphate, testosterone, sex hormone binding globulin, dehydroepiandrosterone sulphate and total alkaline phosphatase. Urine was assayed for calcium, hydroxyproline, oestrone glucuronide and the collagen cross-links pyridinoline and deoxypyridinoline using high-performance liquid chromatography. Bone density was measured at the lumbar spine and femoral neck using dual photon absorptiometry at time 0, 12, 24 and 48 months. The mean annual percentage change in bone density (SE) was –1.41% (0.18) at the lumbar spine and –0.86% (0.22) at the femoral neck. There was no evidence of bimodality or a fast loser subgroup as the rates of change were normally distributed. Both simple and multiple stepwise regression analyses revealed no significant correlation between the rates of change in bone density with any biochemical marker, either individually or in combination, despite the study having sufficient power (80%) to detect a correlation of 0.5 between any biochemical marker levels and bone loss. We conclude that single measurements of these markers of bone turnover and endogenous sex hormones appear unlikely to be clinically useful in predicting early postmenopausal bone loss from either the spine or the hip.     

Correlations between periodontitis and loss of mandibular bone in relation to systemic bone changes in postmenopausal Japanese women

A new method of measuring mandibular alveolar bone mineral density (BMD) was applied to 40 postmenopausal Japanese women aged 50–69 years exhibiting minimal to mild periodontal diseases. Lumbar spine BMD was measured by dual X-ray absorptiometry (DXA) and calcaneus speed of sound (SOS) by quantitative ultrasound (QUS). There were age-related decreases of alveolar BMD, calcaneus SOS and vertebral BMD. There were significant correlations between two of the respective bone mass values. Correlations between clinical dental findings and bone mass data including alveolar BMD, SOS and lumbar spine BMD were investigated. Significant correlations were demonstrated between alveolar BMD and calcaneus SOS or vertebral BMD. Alveolar BMD showed significant correlation with clinical dental findings including periodontal pocket depth and mobility as well as calcaneus SOS and lumbar spine BMD. Using multivariate analysis combinations of univariate predictors, including deoxypyridinoline (DPD), significantly predicted attachment levels. The SOS value was useful combined with other predictors for predicting attachment level. It was concluded that the new method of evaluating alveolar BMD is useful to predict systemic bone mass and strength as well as dental clinical findings.     

Clinical utility of (18)F-fluoride PET/CT in benign and malignant bone diseases

¹⁸F labeled sodium fluoride is a positron-emitting, bone seeking agent with more favorable skeletal kinetics than conventional phosphate and diphosphonate compounds. With the expanding clinical usage of PET/CT, there is renewed interest in using ¹⁸F-fluoride PET/CT for imaging bone diseases. Growing evidence indicates that ¹⁸F fluoride PET/CT offers increased sensitivity, specificity, and diagnostic accuracy in evaluating metastatic bone disease compared to ^99mTc based bone scintigraphy. National Oncologic PET Registry (NOPR) has expanded coverage for ¹⁸F sodium fluoride PET scans since February 2011 for the evaluation of osseous metastatic disease. In this article, we reviewed the pharmacological characteristics of sodium fluoride, as well as the clinical utility of PET/CT using ¹⁸F-fluoride in both benign and malignant bone disorders.     

Seasonal variation of lumbar spine bone mineral content in normal women

Summary The seasonal influence on lumbar spine bone mineral was evaluated in a prospective study of 26 normal women aged 19–66 years. Bone mineral content of the second, third, and fourth lumbar vertebrae (lumbar BMC) was determined every 3 months during 1 year by using dual-photon (¹⁵³Gd) absorptiometry. Lumbar BMC was, on an average (mean±SE), 0.86±0.27 arbitrary units or 1.7±0.5% higher in July to September than in January to March (P<0.005), when other sources of variation were eliminated. It is hypothesized that the seasonal variation in lumbar spine bone mineral reflects differences of the mechanical loading on the vertebrae. The interpretation of longitudinal studies of lumbar BMC may be erroneous if the seasonal variations in bone mineral are not considered.     

Effect of intranasal salmon calcitonin therapy on bone mass and bone turnover in early postmenopausal women: A dose-response study

We examine the dose-related effect of intranasal salmon calcitonin (sCT) on the early postmenopausal bone loss and bone turnover; a 2-year, prospective, randomized, double-blind, placebo-controlled study was carried out with 134 healthy women who had passed a natural menopause within 6 months to 3 years. The women were allocated randomly to 2 years of treatment with either 100, 200, or 400 IU of sCT given intranasally or placebo. All groups received a calcium supplement of 500 mg. Twenty-one women left the study before its end and 91 complied with the study criteria throughout. Bone mineral content/density of the distal forearm and lumbar spine and biochemical parameters of bone turnover were measured. Although the measurements after 24 months revealed no significant difference between groups in bone mineral density of the lumbar spine, the average changes over time revealed prevention of bone loss in the groups treated with 200 and 400 IU of sCT (0.2 to-0.6%) and declines of 0.8-1.7% in the groups treated with 100 IU of sCT and placebo (P<0.05–0.01; within-group testing). There was no dose-related response to sCT but there was a significant difference between the pooled groups treated with 200 plus 400 IU of sCT versus the 100 IU sCT and placebo-treated groups (P=0.030–0.005). The same difference between groups was seen for biochemical parameters of bone turnover (P=0.022–0.003). The biochemical parameters of bone turnover revealed decreases of 10–20% (P<0.001; within group testing) in the groups treated with the two highest sCT doses. It was concluded that nasal sCT in doses of 200 and 400 IU has some effect in women soon after the menopause—preventing the bone loss in the spine throughout the first year of therapy and lowering the bone turnover. It may be used as an alternative to hormone replacement when estrogens are contraindicated. The present data indicate that discontinuous strategies should be preferred.     

The relation between lifestyle factors and biochemical markers of bone turnover among early postmenopausal women

We examined the associations of two biochemical markers of bone turnover with lifestyle factors in 340 postmenopausal women in Hawaii, ages 45–59 years, from the Early Postmenopausal Intervention Cohort. Physical activity, calcium supplement use, smoking and alcohol use in the prior 2 weeks were measured and examined as independent variables in multiple regression analyses with bone turnover markers as dependent variables, adjusted for weight, height, whole body bone mass, serum estradiol, years since menopause, and ethnicity. Calcium supplement and alcohol use were significantly associated with reduced levels of urinary type I collagen cross-linked N-telopeptides (NTX). The mean NTX level was 12% lower among women using ≥250 mg of calcium supplements per day as compared with other women, and 20% lower among alcohol users compared with nonusers. Both calcium supplement use and alcohol intake were associated with lower mean serum osteocalcin (a marker of bone formation) and NTX z-scores. By contrast, smoking was associated with lower osteocalcin levels, without any effect on NTX. The osteocalcin level was 12% lower among smokers compared with nonsmokers. In addition, the z-score difference between NTX and osteocalcin was significantly associated with smoking, with a shift towards more NTX than osteocalcin. Physical activity was not significantly associated with either of the markers. These findings suggest that biochemical markers may help to identify lifestyle factors that affect bone, and provide estimates of the relative magnitude of these effects on bone formation and resorption, independent of each other.     

绝经后妇女血清OPN水平与骨密度及骨转换水平的相关性研究

目的：研究绝经后女性血清骨桥蛋白（OPN）水平与骨密度（BMD）、骨标志物的关系,探索OPN在绝经后骨质疏松症（ PMOP）中的临床应用价值。方法对125名绝经后女性进行研究,双能X线骨密度仪测量腰1－4及左股骨颈BMD,测定血中I型原胶原N－端前肽（PINP）、β－胶原降解产物（β－CTX）、25羟维生素D、甲状旁腺素、OPN、骨钙素（OC）、钙（Ca）和磷（P）。结果①骨质疏松组血清OPN水平明显高于骨量减少和正常组（ F＝0．118,P＝0．000）;②血清OPN水平与BMD（腰1－4,左股骨颈）、血Ca显著负相关,与年龄、β－CTX、OC显著正相关（ P均＜0．05）;③多元线性回归分析结果表明,左股骨颈骨密度（B,－11．971;SE,2．383;标准系数,－0．402;P＝0．000）、血钙（B,－6．696;SE,2．383;标准系数,－0．225;P＝0．006）是OPN水平独立预测因子。结论高血清OPN水平与低BMD、高β－CTX水平及钙缺乏相关,该结果丰富了现有的临床证据,为防治PMOP提供了新的思路。     

Age-dependent effects of atorvastatin on biochemical bone turnover markers: a randomized controlled trial in postmenopausal women

The use of HMG-CoA-reductase inhibitors (statins) has been associated with decreased risk of bone fractures in epidemiological studies. In vitro evidence suggests that statins may stimulate bone formation, but the data are still preliminary. We assessed the effects of the HMG-CoA-reductase inhibitor atorvastatin on biochemical parameters of bone metabolism in a multicenter, randomized, double-blind, placebo-controlled trial conducted between October 2001 and October 2002 in three hospital-based outpatient metabolism clinics. Forty-nine postmenopausal women, mean age 61 ± 5 years, mean time postmenopause 12.6 ± 8.8 years, were treated with atorvastatin, 20 mg per day (n=24) or matching placebos (n=25) for 8 weeks. Comparing the differences to baseline between the groups, there were no statistically significant effects of atorvastatin either on the bone formation markers intact osteocalcin and bone-specific alkaline phosphatase or on the bone resorption markers C-telopeptide and intact parathyroid hormone. The marker of bone fractures, undercarboxylated osteocalcin, was also unchanged. When analyzed in dependence of age, atorvastatin increased C-telopeptide and osteocalcin in the younger subjects, while it decreased them in older subjects. Most interestingly, in older subjects, atorvastatin caused a significant decrease in the ratio of C-telopeptide to osteocalcin, an indicator of bone remodeling, while the ratio was increased in younger subjects, suggesting beneficial effects on bone turnover exclusively in older individuals (approx. >63 years). In summary, the present data suggest that short-term treatment with atorvastatin may have age-dependent effects on biochemical markers of bone turnover in postmenopausal women.     

Hormonal profiles and biochemical indices of bone turnover in Indian women

Summary The study establishes Indian referent database for bone turnover markers. The levels of markers decreased across the four quartiles of BMD showing a negative correlation with BMD. The study depicts that levels of hormones and bone turnover makers can aid in identifying women at risk for osteoporosis. Introduction Biochemical markers of bone turnover reflect changes in bone metabolism earlier and aid in the management of osteoporosis. Since a referent database for Indian women is lacking, the study was initiated to establish the same and suggest that hormonal profiles and markers of bone turnover can aid in identifying women at risk for osteoporosis. Methods Osteocalcin (OC), bone specific alkaline phosphatase ((BSAP), C-terminal crosslinking telopeptide of type-I collagen (CTX-I), deoxypyridinoline (DPD), follicle-stimulating hormone (FSH) and estrone glucuronide (E₁G) were measured in 365 Indian women (20–70 years) and correlated with BMD measurements by dual energy absorptiometry (DXA) using one way analysis of variance (ANOVA). Results The mean levels of bone resorption markers; CTX-I and DPD increased significantly across the age showing a negative correlation with BMD. The increase in levels of CTX-I and DPD was significantly higher (p < 0.0001) as compared to the femoral and spinal BMD, which dropped only 30–36%. The levels of bone turnover markers and FSH decreased across the four quartiles of spinal and femoral BMD showing a negative correlation whereas E₁G levels increased across the four quartiles. Conclusion The bone turnover markers were comparatively low in cohort of Indian women studied.     

Short-term menatetrenone therapy increases gamma-carboxylation of osteocalcin with a moderate increase of bone turnover in postmenopausal osteoporosis: a randomized prospective study

The effect of vitamin K₂ (menatetrenone) on bone turnover was investigated in postmenopausal patients with osteoporosis. A 6-month open-label, randomized prospective study was conducted in 109 patients. The control group (n = 53) received calcium aspartate (133.8 mg of elemental calcium daily), while the menatetrenone group (n = 56) received 45 mg of menatetrenone daily for 6 months. Serum and urinary levels of bone turnover markers were monitored. The serum level of undercarboxylated osteocalcin (uc-OC) was significantly lower (P < 0.001) in the menatetrenone group than in the control group (at 1 month), while there was a higher level of osteocalcin containing gamma-carboxylated glutamic acid (Gla-OC) in the menatetrenone group than the control group (P = 0.018). Significant differences of uc-OC and Gla-OC between the two groups were observed from 1 month onward. In addition, a higher level of intact osteocalcin was found in the menatetrenone group compared with the control group after 6 months (P = 0.006). Assessment of bone resorption markers showed that menatetrenone therapy was associated with significantly higher urinary N-telopeptide of type I collagen (NTX) excretion compared with the control group after 6 months, while there was no significant difference of urinary deoxypyridinoline excretion between the two groups. In conclusion, one month of menatetrenone therapy enhanced the secretion and gamma-carboxylation of osteocalcin, while urinary NTX excretion was increased after 6 months of treatment. Further investigations are required to determine whether the effects of menatetrenone on bone turnover are associated with fracture prevention.     

The effect of low-dose cyclical etidronate and calcium on bone mass in early postmenopausal women

This 2-year study was carried out in 36 healthy women of mean age 53.9±3.8 (SD) years and 3.4±2.3 years postmenopausal. Bone mineral density (BMD) in the spine, measured by single-energy quantitative computed tomographic scanning, gave a mean initial value of 110±26 mg/ml. The women were divided randomly into group 1 (n=11), calcium 600 mg/day; group 2 (n=15), calcium plus etidronate sodium 400 mg/day for 14 days every 3 months; and group 3 (n=10), calcium plus etidronate plus phosphate, the 14-day etidronate course being preceded by phosphate 1 g twice daily for 3 days. During the first year of the study BMD decreased by 6.0±5.8% (p<0.005) in group 1 subjects and increased by 4.5±7.8% (p<0.005) in the combined etidronate-treated groups (difference between control and treatedp<0.001). Inclusion of phosphate in the regimen did not affect the response to etidronate. In the second year there was no significant mean change in BMD in any of the three groups. However, whilst there was little change in BMD values for most of the group 1 subjects, there was considerable variation in individual response within the etidronate-treated groups, with some subjects gaining and some losing bone. The change in BMD during the second year in the subjects as a whole was highly correlated with the change in plasma calcium after 3 months of treatment (r=0.60,p<0.001). Low-dose cyclical etidronate prevents postmenopausal bone loss during the first year of its administration, but was no more effective than calcium supplements during the second year. The positive correlation between early change in plasma calcium and second-year change in BMD, and the reduced bone loss in the second year in the subjects having only calcium supplements, are consistent with a beneficial effect of calcium supplements.     

The effects of <Emphasis Type="Italic">Acanthopanax senticosus</Emphasis> extract on bone turnover and bone mineral density in Korean postmenopausal women

The purpose of this prospective randomized study was to investigate the effects of the extract of Acanthopanax senticosus (AS extract), a widely used oriental herb, on bone remodeling and bone mineral density in Korean postmenopausal women. A total of 81 postmenopausal women with osteopenia or osteoporosis, an age of less than 65 years, were enrolled in the study. Subjects were randomly assigned to two groups: (1) the control group (n = 40), calcium intake (500 mg per day), and (2) the treatment group (n = 41), calcium (500 mg per day) plus AS extract (3 g per day). After treatment with AS extract for 6 months, the AS extract group showed a significant increase in serum osteocalcin levels compared with the control group (P = 0.041). However, no significant changes in bone mineral density were observed by dual-energy X-ray absorptiometry (DXA). AS extract was generally well tolerated, and no differences were observed between the two groups in terms of adverse events. This study suggests that AS extract supplementation may have beneficial effects on bone remodeling in Korean postmenopausal women and that it has no significant adverse events.     

Differences in hip quantitative computed tomography (QCT) measurements of bone mineral density and bone strength between glucocorticoid-treated and glucocorticoid-naïve postmenopausal women

Chronic treatment with glucocorticoids (GCs) leads to significant bone loss and increased risk of fractures. In chronically GC-treated patients, hip fracture risk is nearly 50%. The purpose of this investigation was to determine if there are differences in the quantities of trabecular and cortical bone and bone strength of the hip between GC-treated osteoporotic patients and controls. Methods: Study subjects were GC-treated osteoporotic postmenopausal women, and controls were postmenopausal women, recruited for separate clinical trials. Quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA) of the hip were obtained from all subjects. QCT outcome variables measured included total, cortical, and trabecular BMD of hip subregions (femoral neck and trochanter) and total hip. In addition, finite element modeling (FEM) was performed on a subset of 19 cases and 38 controls, matched on age (± 5 years), weight (± 5 kg), and history of hormone replacement (>1 year use) to assess failure load in stance and fall loading conditions. Generalized linear models were used to adjust the QCT variables for covariates between groups. Multiple regression was performed to identify independent predictors of bone strength from the QCT variables. Results: Compared with controls, GC-treated subjects were significantly (p<0.05) younger, weighed less, and had more years of hormone replacement. QCT of the hip in GC-treated subjects for total femoral integral, cortical, and trabecular BMD averaged 4.9–23.2% (p<0.002) less than controls, and similar results were seen by hip subregion including the trochanter and femoral neck. DXA of the total hip was 17% lower in GC subjects than controls (p<0.05). Compared with controls, FEM failure load in GC subjects was 15% (p<0.05) and 16% (p=0.07) lower for stance and fall loading conditions, respectively. Multiple regression analysis demonstrated that a combination of QCT measures was correlated with bone strength as measured by FEM. Conclusions: Chronic GC treatment in postmenopausal women resulted in significantly decreased BMD of the hip, measured by QCT, with loss of both trabecular and cortical bone. In addition, GC treatment decreased bone strength as determined by FEM. The reduced cortical and trabecular bone mass in the hip may contribute to the disproportionately high hip fracture rates observed in GC-treated subjects.This work was supported by grants from the NIH 1R01AG05407, 1R01AR40431, 1R01AR46197, the Doris Duke Clinical Research Fellowship (CRF) Program for Medical Students (#20000684) K24AR048841-02 and the Rosalind Russell Arthritis Foundation.     

绝经后妇女骨质疏松性椎体骨折与腰椎骨密度的关系

目的探讨绝经后妇女骨质疏松性椎体骨折与腰椎骨密度的关系。方法选择骨质疏松性椎体骨折的绝经后妇女23例为骨折组,无椎体骨折的25例绝经后骨质疏松妇女为对照组。两组的年龄、绝经年限、身高、体重、体重指数差异无显著性,均行胸腰椎正侧位X线摄片。用双能X线吸收仪（DXA）测量的腰椎（L2-4）前后位骨密度（BMD）、骨矿含量（BMC）和T值。结果骨折组BMD、BMC和T值均低于对照组（P〈0.01）。结论腰椎BMD降低与绝经后妇女的骨质疏松性椎体骨折相关。绝经后骨质疏松妇女应重视BMD变化,预防椎体骨折的发生。     

Higher circulating hsCRP levels are associated with lower bone mineral density in healthy pre- and postmenopausal women: evidence for a link between systemic inflammation and osteoporosis

Factors involved in inflammation are linked with those critical for bone remodeling. We examined the association between serum high sensitivity C-reactive protein (hsCRP) levels and bone mineral density (BMD) in healthy women. Serum concentrations of hsCRP and total alkaline phosphatase (ALP) were measured in premenopausal ( n =3,662) and postmenopausal ( n =1,031) women aged 30 years or older. BMD was measured at the femoral neck and lumbar spine using dual energy X-ray absorptiometry. According to the WHO definition, osteopenia was diagnosed at –2.5< T -score <–1.0 SD, and osteoporosis was diagnosed at T -score –2.5 SD at any sites. Compared with normal subjects, log-transformed serum hsCRP levels were higher in osteopenic and osteoporotic subjects (all, P <0.001) with linearity ( P for trend <0.001), after adjustment for age, BMI and menopausal status. Menopausal status did not have a significant interaction on the association ( P =0.457). In both premenopausal and postmenopausal women, serum total ALP levels were higher in the subjects with higher hsCRP quintiles than those with the lowest quintile (all, P for trend <0.001). Multivariate-adjusted odds ratio (OR) for osteoporosis and osteopenia were 1.35 (95% CI, 1.08 to 1.68) in the highest hsCRP quintile of premenopausal women, and OR for osteoporosis was 1.54 (95% CI, 1.10 to 2.53) in the highest hsCRP quintile of postmenopausal women. These findings suggest that subclinical systemic inflammation may be associated with bone turnover rate and bone mass in healthy women.     

围绝经期及绝经后妇女骨量变化规律的初步分析

目的了解广东省围绝经期及绝经后妇女的骨量变化规律及特点，并分析妇女骨量的有关影响因素，为妇女骨质疏松症的防治提供科学依据。方法在广东居住10年以上的妇女214例，均接受腰椎和股骨上端骨密度测定，并对测量结果进行统计分析。结果妇女腰椎和髋部的骨密度值自围绝经期即开始缓慢下降，绝经以后下降速度加快，其中绝经后前4年内下降迅速，以后则相对缓慢。同时，体重和生育次数可以影响妇女骨密度值。结论妇女各部位骨密度值从围绝经期开始即有不同程度的下降，因此早期对敏感部位进行骨密度检测，并早期治疗，有利于预防骨质疏松性骨折。     

Exercise maintains bone density at spine and hip EFOPS: a 3-year longitudinal study in early postmenopausal women

It is an important aim in the prevention of osteoporosis to stop or decelerate bone loss during the early postmenopausal years. Here we report on results of the 3-year EFOPS exercise trial in osteopenic women. The exercise strategy emphasized low-volume high-resistance strength training and high-impact aerobics. Forty-eight fully compliant women (55.1±3.3 years) with no medication or illness affecting bone metabolism participated in the exercise group (EG); 30 women (55.5±3.0 years) served as non-training controls (CG). At baseline there were no significant between-group differences with respect to physical fitness, bone mineral density, pain and nutritional status. The training consisted of two group training and two home training sessions per week. The study participants of both groups were individually supplemented with calcium and vitamin D (cholecalciferol). Bone mineral density (BMD) was measured by DXA at the lumbar spine, proximal femur and distal forearm and by QCT at the lumbar spine. Speed of sound and broadband ultrasound attenuation were determined at the calcaneus by quantitative ultrasound (QUS). Pain frequency and intensity at different skeletal sites were assessed via questionnaire. After 38 months, the following within-group changes were measured: DXA lumbar spine, EG: 0.8% n.s.; CG: –3.3% P <0.001; QCT trabecular ROI, EG: 1.1% n.s; CG: –7.7% P <0.001; QCT cortical ROI, EG: 5.3% P <0.001; CG: –2.6% P <0.001; DXA total hip: EG: –0.2% n.s; CG –1.9%, P <0.001; DXA distal forearm, EG: –2.8% P <0.001; CG: –3.8% P <0.001; BUA, EG: –0.3% n.s; CG –5.4% P <0.001; SOS, EG: 0.3% n.s; CG –1.0% P <0.001. At year 3 between-group differences relative to the exercise group were: DXA lumbar spine: 4.1% P <0.001; QCT trabecular ROI: 8.8% P <0.001; QCT cortical ROI: 7.9% P <0.001; DXA total hip: 2.1%, P <0.001; DXA distal forearm: 1.0% n.s.; BUA: 5.8% P <0.05; SOS: 1.3% P <0.001. Pain frequency and intensity in the spine significantly decreased in the exercise group and increased in the control group, while no between-group differences were detected in the main joints. In summary, over a period of 3 years our low-volume/high-intensity exercise program was successful to maintain bone mineral density at the spine, hip and calcaneus, but not at the forearm.     

Potential for bone turnover markers to cost-effectively identify and select post-menopausal osteopenic women at high risk of fracture for bisphosphonate therapy

Introduction and hypothesis Over half of all fractures among post-menopausal women occur in those who do not have osteoporosis by bone density criteria. Measurement of bone turnover may cost-effectively identify a subset of women with T-score >−2.5 for whom anti-resorptive drug therapy is cost-effective. Methods Using a Markov model, we estimated the cost per quality adjusted life year (QALY) for five years of oral bisphosphonate compared to no drug therapy for osteopenic post-menopausal women aged 60 to 80 years with a high (top quartile) or low (bottom 3 quartiles) level of a bone turnover marker. Results For women with high bone turnover, the cost per QALY gained with alendronate compared to no drug therapy among women aged 70 years with T-scores of −2.0 or −1.5 were $58,000 and $80,000 (U.S. 2004 dollars), respectively. If bisphosphonates therapy also reduced the risk of non-vertebral fractures by 20% among osteopenic women with high bone turnover, then the costs per QALY gained were $34,000 and $50,000 for women age 70 with high bone turnover and T-scores of −2.0 and −1.5, respectively. Conclusion Measurement of bone turnover markers has the potential to identify a subset of post-menopausal women without osteoporosis by bone density criteria for whom bisphosphonate therapy to prevent fracture is cost-effective. The size of that subset highly depends on the assumed efficacy of bisphosphonates for fracture risk reduction among women with both a T-score >−2.5 and high bone turnover and the cost of bisphosphonate treatment.     

Daily and intermittent oral ibandronate normalize bone turnover and provide significant reduction in vertebral fracture risk: results from the BONE study

Increasing evidence suggests that a high rate of bone turnover is associated with low bone mineral density (BMD) and is strongly linked to fracture risk. Measurement of biochemical markers of bone turnover is therefore becoming a more widely used endpoint in clinical trials in postmenopausal osteoporosis. This multinational double-blind, fracture-prevention study enrolled 2946 postmenopausal women with osteoporosis. Patients were randomized to receive placebo or oral ibandronate administered daily (2.5 mg/day) or intermittently (20 mg every other day for 12 doses every 3 months). The primary endpoint was the incidence of new vertebral fractures after 3 years. Secondary outcome measures included changes in the rate of bone turnover as assessed by biochemical markers and increases in spinal and hip BMD. Daily and intermittent oral ibandronate significantly reduced the risk of vertebral fractures by 62% and 50%, respectively, and produced significant and sustained reductions in all the measured biochemical markers of bone turnover. By 3 months, the rate of bone turnover was reduced by approximately 50–60%, and this level of suppression was sustained throughout the remainder of the study. In summary, oral ibandronate, given daily or with a between-dose interval of >2 months, normalizes the rate of bone turnover, provides significant increases in BMD and a marked reduction in the incidence of vertebral fractures. Thus, intermittent ibandronate has potential to become an important alternative to currently licensed bisphosphonates in postmenopausal osteoporosis.