Repeated Bone Mineral Density Measurements Research Articles

Apparent "Rapid Loss" After Short-Interval Bone Density Testing in Menopausal Women Is Usually a Measurement Artifact.

Medication may be considered when bone mineral density (BMD) loss is reported as "excessive." We hypothesized that the rate of BMD change between 2 serial tests demonstrates higher random variability at shorter vs longer intervals, misclassifying some women as "rapid losers." This retrospective observational cohort study in Manitoba, Canada included women aged > 55 years without osteoporosis medications or glucocorticoids. Using paired baseline (1998-2016) and repeat (2001-2018) BMD measurements, we estimated the distribution of annualized change (first to second BMD) at spine, hip, and femoral neck stratified by testing interval (2-2.9, 3-3.9,...9-9.9, ≥ 10.0 years). "Rapid annual bone loss" was defined as exceeding the 95th percentile for decreases from all measurement pairs. Odds ratios (OR) for rapid loss were estimated using regression models adjusted for age and clinical covariates. From 7126 paired BMD measurements, mean annualized change was constant yet standard deviations in BMD change were > 2-fold greater with intervals of 2 to 2.9 years vs ≥ 10 years(P < 0.001). "Rapid annual loss" was seen in ~10% of short-interval tests vs < 1% of long-interval tests. ORs for "rapid loss" progressively declined with increasing testing interval (spine 15.3 [4.8-48.9], total hip 9.3 [4.4-19.5], femoral neck 18.7 [6.8-51.3] for a 2- to 2.9-year testing interval; referent ≥ 10 years). There is a wider apparent range in annualized BMD loss with short-interval testing which greatly attenuates over longer intervals. BMD reports of "rapid loss" across shorter testing intervals likely reflect an artifact of BMD measurement error and should not be used as an indication for antifracture medication initiation.

Does radiopaque cement conceal periprosthetic bone loss around femoral stems?

Periprosthetic bone remodelling may increase fracture risk and deplete bone stock around hip implants. These changes are in part caused by implant design, advocating an early evaluation of bone remodelling properties of new implants. This can be done by repeated dual-energy x-ray absorptiometry (DXA) measurements. We know that radiopaque cement falsely elevates bone mineral density (BMD) in single measurements, however, its impact on repeated measurements, i.e. BMD changes is unexplored. We have therefore investigated whether the presence of radiopaque cement affect repeated BMD measurements. 33 patients eligible for total hip replacement were randomly assigned to either radiopaque or radiolucent cement. BMD changes up to 12 months were measured by DXA, in addition to Harris Hip Score, plain radiographs and radiostereometric analysis (RSA). Periprosthetic BMD declined during the first 3-6 months in all zones in both groups. The greatest reduction (14%) was seen in the proximal Gruen zones (1 and 7). We found a significant difference in Gruen zones 1 and 2, where the measured bone loss was higher in the radiolucent cement group. The presence of radiopaque agents in bone cement may influence DXA measurements of bone remodelling.ClinicalTrials.gov identifier NCT00473421.

Impact of Glycaemic Control on Bone Metabolism in Adult Patients with Type 1 Diabetes Mellitus

Introduction: Type 1 diabetes mellitus (T1DM) is associated with reduced bone mineral density (BMD), increased bone turnover and impaired bone microarchitecture. However, data regarding the influence of glycaemic control on bone metabolism are limited. The aim of this study was to evaluate BMD and bone remodeling markers in patients with T1DM in relation to changes in glycaemic control. Methods/Design: We studied 118 patients with T1DM and age 20-50 years (mean 34.6±7.9years, M/F:53/65), diabetes duration &amp;gt;5 years and no diabetic complications and 95 healthy controls matched for age, sex and body mass index (BMI). All T1DM participants were re-examined after one-year (FU). In both groups, measurements of glycated hemoglobin (HbA1c) and BMD at lumbar spine (LS) and femoral neck (FN) by dual energy X-ray absorptiometry (DXA) were performed. Bone resorption and formation was assessed by measurements of β-crosslaps and of type 1 procollagen total N-terminal propeptide (TP1NP) in serum. Currently, seventy T1DM patients completed the FU and had repeat biochemical and BMD measurements. Based on current literature, BMD changes of ≥3% at the LS and of ≥6% at the FN were considered significant. Results: In the T1DM group, mean duration of the disease was 15.9±7.6 years and mean HbA1c was 8.1±1.4%. Subject in the T1DM group had lower BMD and Z-score at LS and FN compared to those in the control group (LS:p=0.039,p=0.02) (FN:p=0.041,p=0.038). At baseline, no significant differences in β-crosslaps and TP1NP were observed between the two groups. Out of the 70 T1DM patient who have completed FU so far, 42/70 patients had ≥0.5% reduction in HbA1c, 12/70 had about the same HbA1c (±0.4%) and 16/70 had ≥0.5% increase in HbA1c. In the 42 patients with improved HbA1c, BMD increased by 3.4% at the LS and by 5.7% at the FN, and TP1NP was significantly higher compared to baseline (p=0.043). Conclusion: T1DM is associated with reduced BMD but improvement of glycaemic control appears to ameliorate BMD and bone turnover. Disclosure E. Barmpa: None. M. Vlychou: None. S. Tigas: None. G.N. Koukoulis: None. A. Bargiota: None.

Effects of analgesics on bone mineral density: A longitudinal analysis of the prospective SWAN cohort with three-group matching weights.

To examine the effects of analgesics on bone mineral density (BMD), which have not been examined in a longitudinal study with multiple measurements. We investigated changes in BMD associated with new use of analgesics in a prospective longitudinal cohort of mid-life women. BMD and medication use were measured annually. We compared BMD among new users of acetaminophen, NSAIDs, and opioids. Adjustment for baseline covariates was conducted through propensity score matching weights. On-treatment analysis was conducted with inverse probability of censoring weights. Analysis based on the initial treatment group was also conducted to provide insights into selection bias. Repeated BMD measurements were examined with generalized estimating equations. We identified 71 acetaminophen new users, 659 NSAID new users, and 84 opioid new users among 2365 participants. In the on-treatment analysis, the opioid group in comparison to the acetaminophen group had an additional average BMD decline of -0.06% [-1.24, 1.11] per year in the spine and -0.45% [-1.51, 0.61] per year in the femoral neck. BMD mean trajectories over time suggested a fifth-year decline in the opioid persistent users compared with other 2 groups. In the initial treatment group analysis, all 3 groups showed similar trajectories. The BMD decline over time was similar among the 3 groups. However, 5years of continuous opioid use may be associated with a greater BMD decline than 5years on other analgesics. Further studies examining the relationship between very long-term persistent opioid use and BMD are warranted.

Fracture prediction from repeat BMD measurements in clinical practice

We investigated whether repeat BMD measurements in clinical populations are useful for fracture risk assessment. We report that repeat BMD measurements are a robust predictor of fracture in clinical populations; this is not affected by preceding BMD change or recent osteoporosis therapy. In clinical practice, many patients selectively undergo repeat bone mineral density (BMD) measurements. We investigated whether repeat BMD measurements in clinical populations are useful for fracture risk assessment and whether this is affected by preceding change in BMD or recent osteoporosis therapy. We identified women and men aged ≥ 50 years who had a BMD measurement during 1990-2009 from a large clinical BMD database for Manitoba, Canada (n = 50,215). Patient subgroups aged ≥ 50 years at baseline with repeat BMD measures were identified. Data were linked to an administrative data repository, from which osteoporosis therapy, fracture outcomes, and covariates were extracted. Using Cox proportional hazards models, we assessed covariate-adjusted risk for major osteoporotic fracture (MOF) and hip fracture according to BMD (total hip, lumbar spine, femoral neck) at different time points. Prevalence of osteoporosis therapy increased from 18 % at baseline to 55 % by the fourth measurement. Total hip BMD was predictive of MOF at each time point. In the patient subgroup with two repeat BMD measurements (n = 13,481), MOF prediction with the first and second measurements was similar: adjusted-hazard ratio (HR) per SD 1.45 (95 % CI 1.34-1.56) vs. 1.64 (95 % CI 1.48-1.81), respectively. No differences were seen when the second measurement results were stratified by preceding change in BMD or osteoporosis therapy (both p-interactions >0.2). Similar results were seen for hip fracture prediction and when spine and femoral neck BMD were analyzed. Repeat BMD measurements are a robust predictor of fracture in clinical populations; this is not affected by preceding BMD change or recent osteoporosis therapy.

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A 66-year-old woman was evaluated for nontraumatic right thigh pain. She had bilateral traumatic femur shaft fractures 27 years ago. She had a history of melanoma resection and a family history of leukemia. She had had osteoporosis for the past 6 years (baseline dual-energy x-ray absorptiometry scan showed a T score of -2.8 at the hip and -2.5 at the lumbar spine). Since then, she had been taking alendronate, 70 mg weekly, while in the care of a rural clinic and had no repeated bone mineral density measurements.

Vitamin D Status and Bone Density in Recently Diagnosed Inflammatory Bowel Disease: The Manitoba IBD Cohort Study

Bone mineral density (BMD) is usually normal at the time of inflammatory bowel disease (IBD) diagnosis. The purpose of this study was to evaluate the role of vitamin D metabolism in recently diagnosed IBD. Adult subjects with recently diagnosed IBD (median 4 yr) were recruited from the University of Manitoba IBD Research Registry into the Manitoba IBD Cohort Study. Baseline BMD and serum 25-hydroxy vitamin D (25OHD) were measured in a nested subgroup of 101 subjects of whom 94 had repeat BMD measurements 2.3 +/- 0.3 yr later. Only a minority (22 [21.8%]) of recently diagnosed IBD participants had optimal serum 25OHD levels (75 nmol/L or greater). Serum 25OHD was positively correlated with baseline BMD for the lumbar spine, total hip, and total body (all P < 0.05). MANOVA confirmed significant between-group differences in baseline T-scores when vitamin D status was categorized according to serum 25OHD quartile (P < 0.05). Gain in total body BMD between the baseline and follow-up DXA scans was positively correlated with 25OHD (r = 0.20, P < 0.05). Poorer vitamin D status correlates with lower baseline BMD at all measurement sites and better vitamin D status is correlated with a gain in total body BMD. Early optimization of vitamin D may play an important role in preventing IBD-related bone disease.

Discordance of longitudinal changes in bone density between densitometers

This study examined the concordance in BMD measurement and longitudinal change in BMD between the GE Lunar Prodigy and GE Lunar DPX. Even though a high concordance between the densitometers was observed on a single measurement occasion, a significant discordance in longitudinal changes in BMD was observed. Introduction Measurement of bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) technology plays an important role in the diagnosis and management of osteoporosis. The present study examined the concordance in BMD measurement and longitudinal change in BMD between GE Lunar Prodigy and DPX. Methods BMD at the lumbar spine and femoral neck was measured in 135 individuals (47 men and 88 women, mean age 73 ± 9 years) using both GE Lunar DPX and Prodigy densitometers at baseline. In this group, 56 individuals (22 men and 34 women) had repeated BMD measurements using the DPX and Prodigy during a subsequent follow-up visit (average duration: 2.2 years). Results For a single BMD measurement, the coefficient of concordance between the Prodigy and DPX was greater than 0.98 at the lumbar spine and 0.96 at the femoral neck, with the slope of linear regression being approximately 1.0. During the period of follow-up, the lumbar spine BMD decreased by − 0.5% (S.D. 1.8%) when measured by DPX, which was significantly different ( p = 0.002) from the change measured by Prodigy (mean change = 0, S.D. 2.0%). However, there was no significant difference ( p = 0.95) in the rate of change in femoral neck BMD measured by DPX (mean = − 1.6%, S.D. = 2.9) and Prodigy (mean = − 1%, S.D. = 1.8%). The correlation in rates of BMD change between Prodigy and DPX was 0.63 at the lumbar spine and 0.52 at the femoral neck. Simulation analysis showed that the theoretical maximum correlation in rates of BMD change between Prodigy and DPX was 0.71. Conclusions Despite both densitometers being highly concordant in a single BMD measurement, discordance in the assessment of BMD changes between the Prodigy and DPX densitometers was observed. These findings have implications regarding the assessment of response to therapy in a multi-centre setting when different densitometers are used.

Evaluating the Value of Repeat Bone Mineral Density Measurement and Prediction of Fractures in Older Women

Whether repeat bone mineral density (BMD) measurement adds benefit beyond the initial BMD measurement in predicting fractures in older women is unknown. We prospectively measured total hip BMD in 4124 older women (mean +/- SD age, 72 +/- 4 years) from 1989 to 1990 and again 8 years later. Incident nontraumatic hip and nonspine fractures were validated by radiology reports (>95% follow-up). In addition, spine fractures were defined morphometrically in 2129 of these women by lateral spine x-ray films from 1991 to 1992 and then again 11.4 years later. Prediction of fracture risk was assessed with proportional hazards models and receiver operating characteristic curves for BMD measures. Over a mean of 5 years after the repeat BMD measure, 877 women experienced an incident nontraumatic nonspine fracture (275 hip fractures). In addition, 340 women developed a spine fracture. After adjustment for age and weight change, initial and repeat BMD measurements were similarly associated with fracture risk (per unit standard deviation lower in BMD) for nonspine (hazard ratio, 1.6), spine (odds ratio, 1.8-1.9), and hip (hazard ratio, 2.0-2.2) fractures (P<.001 for all models). Areas under the receiver operating characteristic curves (AUC) revealed no significant differences to discriminate nonspine (AUC, 0.65), spine (AUC, 0.67-0.68), or hip (AUC, 0.73-0.74) fractures between models with initial BMD, repeat BMD, or initial BMD plus change in BMD. Stratification by initial BMD t scores (normal, osteopenic, or osteoporotic), high bone loss, or hormone therapy did not alter results. In healthy, older, postmenopausal women, repeating a measurement of BMD up to 8 years later provides little additional value besides the initial BMD measurement for predicting incident fractures.

Changes in bone mineral density in transient osteoporosis of the hip

Transient osteoporosis of the hip is a disorder characterised by pain, and associated with temporary osteopaenia. Although osteopaenia is the essence of the condition, data do not exist about the local bone density of the femoral neck if no medication is administered. We describe three patients who were treated with limitation of weight-bearing only. Repeated bone mineral density measurements were obtained, and that at the femoral neck was lowest two months after the onset of the condition. The mean reduction in bone mineral density when compared with an age-matched control group was 13% (3% to 24%). Spontaneous recovery was observed in all patients.

Influence of weight and weight change on bone loss in perimenopausal and early postmenopausal Scottish women.

Weight is recognized as an important factor in determining an individual's risk of osteoporosis. However, little is known about whether weight or weight change influences bone loss around the time of the menopause, and the relationship with energy intake and physical activity level remains largely undefined. Healthy premenopausal women (1,064 selected from a random population of 5,119 women aged 45-54 years at baseline) each had bone mineral density (BMD), weight and height measurements, and completed a food frequency and physical activity questionnaire. Of the original participants, 907 women (85.2%) returned 6.3 +/- 0.6 years later for repeat BMD measurements, and 896 women completed the questionnaires. Bone loss at the hip (FN) and spine (LS) occurred before the menopause. Weight change rather than weight was associated with FN BMD loss (r=0.102, p=0.002), but weight at follow-up was associated with LS BMD change (r=0.105, p=0.002). Although an increase in physical activity level (PAL) appeared to be beneficial for FN BMD in women who were heavy weight gainers, PAL was associated with increased LS BMD loss in women who lost weight. For current HRT users, neither weight nor weight change was associated with change in BMD. Postmenopausal women not taking HRT should be made aware that low body weight or losing weight during this particularly vulnerable period may worsen bone loss.

Risk factors for low bone mineral density and the 6-year rate of bone loss among premenopausal and perimenopausal women.

Risk factors that are associated with lower bone mineral density (BMD) may not necessarily be associated with increased bone loss among premenopausal and perimenopausal women. We determined risk factors for lower premenopausal and perimenopausal BMD while simultaneously determining risk factors for increased 6-year rate of bone loss among women aged 24-50 years within a population-based prospective cohort study. BMD of the lumbar spine and femoral neck, reported as t scores, were measured five times within the 6-year study among 614 women who were between the ages of 24 and 44 in 1992/1993. Rates of bone loss were calculated from the repeated BMD measurements. Risk factors for lower BMD over time at the lumbar spine included history of any fracture ( P=0.005). The major risk factor for lower BMD over time at the femoral neck was family history of osteoporosis ( P<0.002). The major protective factor for greater BMD over time at both skeletal sites was additional body weight ( P<0.0001). Other protective factors for greater BMD over time at the femoral neck were modest alcohol consumption ( P=0.0002) and high-school sports participation ( P=0.002). Risk factors for greater bone loss at either skeletal site included postmenopausal status ( P<0.0001 at the lumbar spine; P=0.01 at the femoral neck), and the reporting of a reproductive cancer ( P<0.0001 at the lumbar spine; P=0.0008 at the femoral neck). Body weight was protective against bone loss at both skeletal sites ( P<0.0001). Baseline age, calcium intake, smoking, and current physical activity were not associated with BMD or bone loss. The understanding of the relative importance of risk factors for both low BMD and bone loss may assist in the identification of women at greater risk for subsequent low postmenopausal BMD.

The precision and influence of rotation for measurements of bone mineral density of the distal femur following total knee arthroplasty: a methodological study using DEXA.

We evaluated the feasibility of DEXA (Norland XR-26 mark II) for quantitative measurements of bone mineral density (BMD) in the lateral plane of the distal femur after total knee arthroplasty (TKA). BMD was measured in 5-6 regions of interest (ROI) in close relation to the femoral component. In an in vitro study using 3 different distal femur phantoms, we found that the precision was affected by rotation of the distal femur. When BMD measurements were repeated within a range of motion of 40 degrees, 20 degrees, and 0 degrees, the coefficient of variation (CV) was approximately 15%, 10%, and 0.6%, respectively. We found that the use of bone cement for implant fixation had no effect on the level of BMD. Double measurements performed in 28 patients gave average CV values of 3.3%, 3.0%, and 2.6% for the uncemented Duracon, and Interax femoral components and the cemented AGC components, respectively. Our in vivo average CV measurements of BMD of the distal femur after TKA were on a level, suitable for repeated BMD measurements in prospective studies, which evaluate adaptive bone remodeling of the distal femur after cemented and uncemented TKA.

Étude comparative de l’efficacité et de la tolérance de l’étidronate et de l’alendronate au cours de l’ostéoporose postménopausique. Influence de l’adjonction d’un traitement hormonal substitutif

Objectives. To compare the efficacy and safety of etidronate and alendronate in patients with postmenopausal osteoporosis and to assess the efficacy of either bisphosphonate in combination with hormone replacement therapy (HRT). Patients and methods. In this pragmatic study, the main efficacy criterion was the mean annual change in bone mineral density (BMD). Patients who had a past or current history of etidronate or alendronate treatment for postmenopausal osteoporosis with at least 18 months follow-up and an evaluation in 1999 were eligible. Recruitment was in an outpatient clinic with a special focus on metabolic bone diseases. Osteoporosis was defined as at least one low-energy fracture or as a lumbar spine or femoral neck BMD decrease to at least 2.5 SD below the mean in young women. HRT was not an exclusion criterion provided treatment duration was longer than one year. Etidronate was given cyclically (14-day courses in a dosage of 400 mg/d separated by 76-day intervals with calcium and vitamin D supplementation) and alendronate was given daily in a dosage of 10 mg/day. Results. Of the 99 patients who met our inclusion criteria, 53 received etidronate (including 23 on HRT) and 46 alendronate (18 on HRT). Repeat BMD measurements were obtained in 88 patients, including 11 who stopped their bisphosphonate therapy within the first year of use because of adverse events. Lumbar spine BMD (mean ±SD) increased significantly both in the etidronate group (+2.1%±0.7%/year) and in the alendronate group (+5.3%±0.9%/year). The increase was significantly greater with alendronate (P<0.01). The lumbar spine BMD increase was largest in the patients on alendronate and HRT (+6.5%±1.4%/year) and was smallest (and nonsignificant) in the patients on etidronate without HRT (+1.2%±0.8%). Femoral neck BMD showed no significant changes in any group. In the intention-to-treat analysis, fractures occurred in 12 etidronate patients (22.6%) and six (13.0%) alendronate patients (nonsignificant). Adverse events requiring bisphosphonate discontinuation before the scheduled date of the follow-up BMD measurement occurred in one patient (1.9%) in the etidronate group (generalized osteomalacia) and in ten patients (21.7%) in the alendronate group (upper or lower gastrointestinal tract symptoms in six and four patients, respectively; P<0.01). Conclusion. Both etidronate and alendronate significantly increased lumbar BMD, but the effect was significantly more marked with alendronate. Conversely, adverse effects, most notably gastrointestinal symptoms, were more common with alendronate, so that premature treatment discontinuation because of adverse events were more common in the alendronate group. Both differences should be taken into account when selecting the best drug for a patient with postmenopausal osteoporosis.

Comparative efficacy and safety study of etidronate and alendronate in postmenopausal osteoporosis. Effect of adding hormone replacement therapy

Objectives. To compare the efficacy and safety of etidronate and alendronate in patients with postmenopausal osteoporosis and to assess the efficacy of either bisphosphonate in combination with hormone replacement therapy (HRT). Patients and methods. In this pragmatic study, the main efficacy criterion was the mean annual change in bone mineral density (BMD). Patients who had a past or current history of etidronate or alendronate treatment for postmenopausal osteoporosis with at least 18 months follow-up and an evaluation in 1999 were eligible. Recruitment was in an outpatient clinic with a special focus on metabolic bone diseases. Osteoporosis was defined as at least one low-energy fracture or as a lumbar spine or femoral neck BMD decrease to at least 2.5 SD below the mean in young women. HRT was not an exclusion criterion provided treatment duration was longer than 1 year. Etidronate was given cyclically (14-day courses in a dosage of 400 mg/d separated by 76-day intervals with calcium and vitamin D supplementation) and alendronate was given daily in a dosage of 10 mg/d. Results. Of the 99 patients who met our inclusion criteria, 53 received etidronate (including 23 on HRT) and 46 alendronate (18 on HRT). Repeat BMD measurements were obtained in 88 patients, including 11 who stopped their bisphosphonate therapy within the first year of use because of adverse events. Lumbar spine BMD (mean ± SD) increased significantly both in the etidronate group (+2.1% ± 0.7%/year) and in the alendronate group (+5.3% ± 0.9%/year). The increase was significantly greater with alendronate ( P < 0.01). The lumbar spine BMD increase was largest in the patients on alendronate and HRT (+6.5% ± 1.4%/year) and was smallest (and nonsignificant) in the patients on etidronate without HRT (+1.2% ± 0.8%). Femoral neck BMD showed no significant changes in any group. In the intention-to-treat analysis, fractures occurred in 12 etidronate patients (22.6%) and six (13.0%) alendronate patients (nonsignificant). Adverse events requiring bisphosphonate discontinuation before the scheduled date of the follow-up BMD measurement occurred in one patient (1.9%) in the etidronate group (generalized osteomalacia) and in ten patients (21.7%) in the alendronate group (upper or lower gastrointestinal tract symptoms in six and four patients, respectively; P < 0.01). Conclusion. Both etidronate and alendronate significantly increased lumbar BMD, but the effect was significantly more marked with alendronate. Conversely, adverse effects, most notably gastrointestinal symptoms, were more common with alendronate, so that premature treatment discontinuation because of adverse events were more common in the alendronate group. Both differences should be taken into account when selecting the best drug for a patient with postmenopausal osteoporosis.

Evaluation of a Fully Automated Serum Assay for C-Terminal Cross-Linking Telopeptide of Type I Collagen in Osteoporosis

Biochemical markers of bone turnover can provide prognostic information about the risk of osteoporotic fracture and are useful tools for monitoring efficacy of antiresorptive therapy. A serum-based automated assay may be of better clinical value than urinary markers because of lower imprecision and day-to-day within-person variability. Our aim was to evaluate the technical and clinical performances of a new, fully automated assay for serum C-terminal cross-linking telopeptide of type I collagen (CTX), a marker of bone resorption. Serum CTX was measured on the Elecsys 2010 automated analyzer (Roche). Results were compared with those of the manual ELISA. We measured serum CTX concentrations in 728 healthy women, ages 31-89 years. We investigated the ability of this assay to predict the rate of postmenopausal forearm bone loss evaluated by four repeated bone mineral density measurements using dual-x-ray absorptiometry in 305 women followed prospectively for 4 years. Finally, in a cohort of healthy, untreated, postmenopausal women, we compared baseline serum CTX in 55 women who subsequently had a fracture (20 vertebral and 35 peripheral fractures) with values in the 380 women who did not fracture during a mean 5 years of follow-up. The within- (n = 21) and between-run (n = 21) CVs were <4.1% and 5.7%, respectively. In 728 healthy women, serum CTX concentrations (automated) correlated with those of the manual ELISA (r = 0.82; P<0.0001). The median long-term within-person variability assessed by four repeated measurements over 3 months in 18 postmenopausal women was 9.4%. Compared with 254 premenopausal women, serum CTX was 39% (P<0.0001) higher in 45 perimenopausal women and 86% (P<0.0001) higher in 429 postmenopausal women (mean age, 64 years). Baseline serum CTX correlated negatively with changes of bone mass measured at the mid (r = -0.23; P<0.0001) and distal (r = -0.27; P<0001) radius. Postmenopausal women with serum CTX greater than the mean + 2 SD values in premenopausal women accounted for 42% of the population, lost bone at the mid radius on average eightfold more rapidly than the other women (-0.27% +/- 2.92% vs. -2.25% +/- 3.95%; P<0.0001), and had increased risk of fracture with a relative risk (95% confidence interval) of 1.8 (1.01-3.1) after adjustment for physical activity. The automated assay for serum CTX is precise and predicts rate of bone loss and fracture risk in postmenopausal women. Because it is convenient to use and has high throughput, this serum bone resorption marker may be useful for the investigation of patients with osteoporosis.

Polymorphism of the vitamin D receptor gene and corticosteroid-related osteoporosis.

Corticosteroid therapy (CST) is associated with reduced intestinal calcium absorption, bone loss and increased fracture risk. As polymorphisms of the vitamin D receptor (VDR) gene may be associated with bone mineral density (BMD) and intestinal calcium absorption, we asked whether patients with a given VDR genotype receiving CST may be at increased or decreased risk for corticosteroid-related bone loss and osteoporosis. We measured areal BMD (g/cm2) by dual-energy X-ray absorptiometry in 193 women (50 premenopausal, 143 postmenopausal) and 70 men with rheumatoid arthritis (n = 44), obstructive airway diseases (n = 128) and other corticosteroid-treated diseases (n = 91). All patients received a cumulative dose greater than 1.8 g per year or a minimum of 5 mg daily of prednisolone or equivalent for at least 1 year. VDR alleles were typed by polymerase chain reaction assay based on the polymorphic BsmI and TaqI restriction sites. BMD in patients was expressed as a Z-score (mean +/- SEM) derived from age- and gender-matched controls. BMD was reduced in patients at the lumbar spine (bb, -0.52 +/- 0.12; Bb, -0.47 +/- 0.11; BB, -0.65 +/- 0.18 SD; p < 0.01), femoral neck (bb, -0.46 +/- 0.10; Bb, -0.34 +/- 0.10; BB, -0.54 +/- 0.14 SD; p < 0.01), Ward's triangle (bb, -0.44 +/- 0.10; Bb, -0.31 +/- 0.10; BB, -0.45 +/- 0.13 SD; p < 0.01), and trochanter (bb, -0.50 +/- 0.10; Bb, -0.30 +/- 0.10; BB, -0.44 +/- 0.14 SD; p < 0.01). However, there was no significant difference in the deficit in BMD in any of the genotypes, either before or after adjusting for age, sex, body mass index, disease type, age at onset of disease, disease duration, cumulative steroid dosage, smoking status and dietary calcium intake. Similarly, there were no detectable differences between the BsmI genotypes and the rate of bone loss in 79 patients with repeated BMD measurements at an interval of 4-48 months. The data suggest that the VDR genotypes may not be a means of identifying patients at greater risk of corticosteroid-related bone loss.

Prediction of Peripheral Fracture Risk by Quantitative Microdensitometry

Background.The purpose of the study was to investigate whether quantitative microdensitometry (QMD) could be used for screening purposes to identify a population with a high risk for peripheral osteoporotic fractures.Methods.In 1984 bone mineral density (BMD) measurements were made on the index finger of 612 women. Repeated BMD measurements were obtained in 1989 in 440 women. Cox proportional hazards models were used to obtain adjusted estimates of the hazard ratio of a fracture according to BMD or bone loss. Receiver operating characteristic curves were constructed and the areas under the curves (AUC) were compared.Results.Thirty-five women experienced peripheral osteoporotic fractures between the first and the second measurement. Women in the three lowest quartiles of bone density were 1.4–1.8 times (diaphyseal site) and 2.4–2.8 times (metaphyseal site) as likely to experience a fracture as those in the highest quartile. Women in the quartile with the highest bone loss had a risk of 6.9 (diaphyseal site) and 7.5 (metaphyseal site) times higher than women in the lowest quartile. The discriminative power of the measurement as a single test was moderate (AUC 63%); two successive measurements, made with an interval of 5 years to measure bone loss, increased the discriminating power (AUC 74%;P< 0.05).Conclusions.Phalangeal BMD and bone loss, as measured by QMD, are important risk factors for peripheral osteoporotic fractures, but cannot be used as an efficient screening instrument for selecting women with the highest fracture risk.

When should bone density measurements be repeated?

We calculated how long to wait before repeating bone mineral density (BMD) measurements to reassess fracture risk. Correlation results from serial measurements of 495 postmenopausal Japanese-American women were used to estimate 95% confidence intervals (CI) for future BMD. After 7 years of follow-up, BMD correlations with the initial measurement ranged between 0.81 and 0.94, depending on age group and measurement site. In this analysis, the period between measurements was defined as the time required for the lower 95% CI to fall below the BMD value corresponding to doubling of fracture risk. Progressive bone loss causes fracture risk to double after 10 years, on average. However, the 95% CIs indicate that a second BMD measurement will detect risk doubling after only 2 or 3 years for some women. For untreated, early postmenopausal women, the period between measurements was approximately 2-5 years for the radius and 4-6 years for the calcaneus, depending on the initial BMD level. The period was approximately 1 year longer for women age 60 and older. Treatments that halve the bone loss rate would increase the period by 1-3 years. In the absence of a second measurement of BMD, the CI will continue to expand with time, corresponding to a wider range in risk between individuals, and a greater proportion of women will be at increased fracture risk. Obtaining a second BMD measurement pinpoints the patient's status within the precision of the measurement. We conclude that repeated BMD measurements will provide a more accurate estimate of fracture risk than a single, baseline measurement.