Annual Rate Of Bone Loss Research Articles

Characteristics of Long-Term Femoral Neck Bone Loss in Postmenopausal Women: A 25-Year Follow-Up.

ABSTRACTThe aim of this study was to monitor long‐term changes in bone mineral density (BMD) after menopause and factors affecting BMD. The study population consisted of a random sample of 3222 women from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study, of which 62.1% were postmenopausal at the beginning of the study. This group of women underwent dual‐energy X‐ray absorptiometry (DXA) measurements at the femoral neck every 5 years from baseline (in 1989) up to 25‐year follow‐up. They also responded to risk‐factor questionnaires at 5‐year intervals. During the 25‐year follow‐up, the baseline cohort decreased to 686 women. The women were divided into quartiles based on their baseline BMD. Self‐reported hormone replacement therapy (HRT) and corticosteroid use were divided into ever users and never users. Morbidity was assessed as the total number of self‐reported diseases and BMD‐affecting diseases. The mean 25‐year BMD change was found to be −10.1%, p < 0.001. Higher baseline BMD was associated with higher bone loss rate; the reduction in the highest quartile BMD was 11.1% and in the lowest quartile 7.4% (p = 0.0031). Lower baseline body mass index (BMI) and a greater increase in BMI were found to protect against postmenopausal bone loss (p < 0.001). The lowest bone loss quartile included 15.2% more HRT users than the highest bone loss quartile (p = 0.004). The number of diseases/bone‐affecting diseases, use of vitamin D/calcium supplementation, use of corticosteroids, smoking or alcohol use had no statistical significance for annual bone loss rate. This study presents hitherto the longest (25‐year) BMD follow‐up in postmenopausal women. The linear femoral neck bone loss of 10% was less than previously assumed. A 5‐year BMD change appeared to predict long‐term bone loss in postmenopausal women. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Reduced Bone Loss Is Associated With Reduced Mortality Risk in Subjects Exposed to Nitrogen Bisphosphonates: A Mediation Analysis.

Bisphosphonates, potent antiresorptive agents, have been found to be associated with mortality reduction. Accelerated bone loss is, in itself, an independent predictor of mortality risk, but the relationship between bisphosphonates, bone loss, and mortality is unknown. This study aimed to determine whether the association between bisphosphonates and mortality is mediated by a reduction in the rate of bone loss. Participants from the population-based Canadian Multicentre Osteoporosis Study were followed prospectively between1996 and 2011. Comorbidities and lifestyle factors were collected at baseline and bone mineral density (BMD) at baseline and at years 3 (for those aged 40 to 60 years), 5, and 10. Rate of bone loss was calculated using linear regression. Information on medication use was obtained yearly. Bisphosphonate users grouped into nitrogen bisphosphonates (nBP; alendronate or risedronate) and etidronate and non-users (NoRx) were matched by propensity score, including all baseline factors as well as time of treatment. Cox's proportional hazards models, unadjusted and adjusted for annual rate of bone loss, were used to determine the association between nBP and etidronate versus NoRx. For the treatment groups with significant mortality risk reduction, the percent of mortality reduction mediated by a reduction in the rate of bone loss was estimated using a causal mediation analysis. There were 271 pairs of nBP and matched NoRx and 327 pairs of etidronate and matched NoRx. nBP but not etidronate use was associated with significant mortality risk reduction (hazard ratios [HR] = 0.61 [95% confidence interval 0.39-0.96] and 1.35 [95% CI 0.86-2.11] for nBP and etidronate, respectively). Rapid bone loss was associated with more than 2-fold increased mortality risk compared with no loss. Mediation analysis indicated that 39% (95% CI 7%-84%) of the nBP association with mortality was related to a reduction in the rate of bone loss. This finding provides an insight into the mechanism of the relationship between nBP and survival benefit in osteoporotic patients. © 2019 American Society for Bone and Mineral Research.

Letter to the Editor.

Letter to the Editor.

Population-based opportunistic osteoporosis screening: Validation of a fully automated CT tool for assessing longitudinal BMD changes.

The automated BMD tool was retrospectively applied to non-contrast abdominal CT scans in 1603 consecutive asymptomatic adults (mean age, 55.9 years; 770 M/833 F) undergoing longitudinal screening (mean interval, 5.7 years; range, 1.0-12.3 years). The spinal column was automatically segmented, with standardized L1 and L2 anterior trabecular ROI placement. Automated and manual L1 HU values were compared, as were automated supine-prone measures. L1-L2 CT attenuation values were converted to BMD values through a linear regression model. BMD values and changes were assessed according to age and gender. Success rate of the automated BMD tool was 99.8 % (four failed cases). Both automated supine vs prone and manual vs automated L1 attenuation measurements showed good agreement. Overall mean annual rate of bone loss was greater in females than males (-2.0% vs -1.0%), but the age-specific rate declined faster in females from age 50 (-2.1%) to age 65 (-0.3%) compared with males (-0.9% to -0.5%). Mean BMD was higher in females than males at age 50 (143.6 vs 135.1 mg cm-3), but post-menopausal bone loss in females reversed this relationship beyond age 60. By age 70, mean BMD in females and males was 100.8 and 107.7 mg cm-3 , respectively. This robust, fully automated CT BMD tool allows for both individualized and population-based assessment. Mean BMD was lower in men than women aged 50-60, but accelerated post-menopausal bone loss in women resulted in lower values beyond age 60. This fully automated tool can be applied to routine abdominal CT scans for prospective or retrospective opportunistic BMD assessment, including change over time. Mean BMD was lower in men compared with women aged 50-60 years, but accelerated bone loss in women during this early post-menopausal period resulted in lower BMD values for women beyond age 60.

Depression and risk of fracture and bone loss: an updated meta-analysis of prospective studies.

The association between depression and risk of fracture remains controversial. We conducted a comprehensive meta-analysis to examine the effect of depression on the risk of osteoporotic fractures and bone loss. We searched databases and reviewed citations in relevant articles for eligible cohort studies. Two investigators independently conducted study selection, appraisal, and data abstraction through the use of a standardized protocol. Random effect models were used for meta-analysis. Cochrane Q and I2 statistics were used to assess heterogeneity. Funnel plots and rank correlation tests were used to evaluate publication bias. Twenty-three studies were included for meta-analysis. In studies that reported hazard ratio (HR) as the outcome (nine studies [n = 309,862]), depression was associated with 26% increase in fracture risk (HR = 1.26, 95% CI, 1.10-1.43, p < 0.001). Studies that reported risk ratio (RR) as the outcome (seven studies [n = 64,975]) suggested that depression was associated with 39% increase in fracture risk (RR = 1.39, 95% CI, 1.19-1.62, p < 0.001). Among studies that reported hip bone mineral density (BMD) as an outcome (eight studies [n = 15,442]), depression was associated with a reduced mean annual bone loss rate of 0.35% (0.18-0.53%, p < 0.001). The increased risk of fracture and bone loss associated with depression was consistent in all meta-analysis having modified inclusion criteria and in different subgroup analyses as well. Significant heterogeneity was observed in the meta-analysis; however, no significant publication bias was detected. Depression is associated with a significant increased risk in fracture and bone loss. Effective prevention may decrease such risk.

Thoracic Quantitative Computed Tomography (QCT) Can Sensitively Monitor Bone Mineral Metabolism: Comparison of Thoracic QCT vs Lumbar QCT and Dual-energy X-ray Absorptiometry in Detection of Age-relative Change in Bone Mineral Density

Sensitive detection of bone mineral density (BMD) change is a key issue to monitor and evaluate the individual bone health status, as well as bone metabolism and bone mineral status. The ability to use thoracic quantitative computed tomography (QCT) to detect the annual change of BMD remains unclear. We aimed to investigate the sensitivity in detecting age-related bone mineral loss using the thoracic QCT from the electrocardiographically gated heart scans in comparison to whole-body dual-energy X-ray absorptiometry (DXA) and standard lumbar QCT. A total of 121 asymptomatic patients' imaging data, including DXA whole body scan, cardiac CT scan, and abdomen scans were analyzed. The BMD of the thoracolumbar spine, upper, and lower extremities were measured using QCT and DXA, respectively. The age-related annual rate of bone density loss was computed and compared to the thoracic and lumbar QCT, as well DXA measures. The age-related annual rate of bone loss with QCT was -0.70 mg/mL3 (-0.75%/y) in women, -0.83 mg/mL3 (-0.86%/y) in men in the thoracic and the lumbar trabecular QCT, respectively. Compared to the QCT, DXA demonstrates a lower annual rate of bone loss in the area of BMD measurement (P < .05 in all, excluding legs of women) in -0.45, -0.42, -0.67, and -0.46 in women, in -0.32, -0.02, -0.12, and -0.08 in men for thoracic, lumbar, leg, and arm, respectively. We conclude that the thoracic and the lumbar QCT provide a similar and more sensitive method for detecting bone mineral loss when compared to DXA.

The Relationship of Serum Serotonin Levels to the Rate of Bone Loss and Fractures in Men

Recent genetic studies in rodents have revealed that circulating serotonin plays a key role in regulating bone formation and skeletal mass. However, the reported effects of circulating serotonin on bone mass in humans have been conflicting. We determined whether circulating serotonin levels influenced the rate of bone loss and fractures in men. We assessed the effect of serum serotonin on bone loss rate in a population-based cohort of 202 ambulatory men aged 56–70 years who were followed up for a median duration of 3.7 years. Serum serotonin levels were assayed, and the Timed Up and Go Test (TUGT) was performed, at baseline. Dual-energy X-ray absorptiometry was performed both at baseline and during follow-up. Fracture prevalence was assessed using questionnaires. The serotonin levels were inversely associated with the lumbar spine bone mineral density (r = −0.174, p = 0.028) at baseline. No association was evident between the bone mineral densities of the femoral neck or total hip and serotonin level. The annual rates of bone loss from the lumbar spine, the femoral neck, and the total hip were 0.01%, 0.46%, and 0.46%, respectively. The baseline serum serotonin level did not predict the bone loss rate in any skeletal site. Lower limb disability evident upon TUGT at baseline predicted bone loss from the total hip. No significant difference of serotonin level was observed between subjects with and without fractures. The serum serotonin level was not associated with the rate of bone loss in elderly men. Thus, the circulating serotonin level does not reliably predict bone loss.

Effect of Precision on Longitudinal Follow-Up of Bone Mineral Density Measurements in Elderly Women and Men

Precision error of dual-energy X-ray absorptiometry exceeds the expected annual rate of bone loss in the elderly. The capacity to detect changes in areal bone mineral density (aBMD; g/cm 2) over a 5-yr period was assessed. Six hundred ninety-one women, 75.2 (0.1) yr, from the Malmö OPRA-study, were measured using Lunar DPX-L (GE Lunar, Madison, WI), and 211 men, 74.7 (3.2) yr, from the Malmö Mr Os-study, were measured using Lunar Prodigy (GE Lunar) with follow-up 5 yr later. Precision error was determined with 30 degrees of freedom. Least significant change (LSC, i.e., 2.77 × precision error) was calculated. Women's precision errors (g/cm 2) for DPX-L were 0.028 (total hip [TH]) and 0.016 (lumbar spine [LS]), and for Prodigy, they were 0.009 (TH) and 0.039 (LS). In men, corresponding results for Prodigy were 0.014 and 0.031. In women, 41% and in men, 39% had aBMD changes exceeding the LSC at TH. Follow-up intervals (i.e., LSC/median rate of aBMD change) for both women and men were 8 yr (TH) and 13 yr (LS). Based on Prodigy precision data, follow-up intervals for women were 3 and 32 yr at TH and LS. In summary, several years were needed to detect change. Only when a high rate of bone loss is suspected, a short follow-up time is possible, in elderly persons.

Age-dependence of femoral strength in white women and men

Although age-related variations in areal bone mineral density (aBMD) and the prevalence of osteoporosis have been well characterized, there is a paucity of data on femoral strength in the population. Addressing this issue, we used finite-element analysis of quantitative computed tomographic scans to assess femoral strength in an age-stratified cohort of 362 women and 317 men, aged 21 to 89 years, randomly sampled from the population of Rochester, MN, and compared femoral strength with femoral neck aBMD. Percent reductions over adulthood were much greater for femoral strength (55% in women, 39% in men) than for femoral neck aBMD (26% in women, 21% in men), an effect that was accentuated in women. Notable declines in strength started in the mid-40s for women and one decade later for men. At advanced age, most of the strength deficit for women compared with men was a result of this decade-earlier onset of strength loss for women, this factor being more important than sex-related differences in peak bone strength and annual rates of bone loss. For both sexes, the prevalence of “low femoral strength” (<3000 N) was much higher than the prevalence of osteoporosis (femoral neck aBMD T-score of −2.5 or less). We conclude that age-related declines in femoral strength are much greater than suggested by age-related declines in femoral neck aBMD. Further, far more of the elderly may be at high risk of hip fracture because of low femoral strength than previously assumed based on the traditional classification of osteoporosis. © 2010 American Society for Bone and Mineral Research.

Association Between Changes in Habitual Physical Activity and Changes in Bone Density, Muscle Strength, and Functional Performance in Elderly Men and Women

To investigate the long-term effects of habitual physical activity on changes in musculoskeletal health, functional performance, and fracture risk in elderly men and women. Ten-year prospective population-based study. Malmö-Sjöbo Prospective Study, Sweden. Participants were 152 men and 206 women aged 50, 60, 70, and 80 who were followed for 10 years. Distal radius bone mineral density (BMD) (single photon absorptiometry), upper limb muscle (grip) strength, balance, gait velocity, occupational and leisure-time activity, and fractures (interview-administered questionnaire) were reassessed after 10 years. Annual changes for all measures were compared between participants with varying habitual physical activity histories at baseline and follow-up: inactive-inactive (n=202), active-inactive (n=47), inactive-active (n=49), and active-active (n=60). Data for men and women were pooled, because there were no sex-by-activity group interactions. To detect possible differences in fracture incidence between the varying habitual activity groups, participants were classified into two activity groups based on their activity classification at baseline and follow-up: inactive:less active versus active:more active. The annual rate of bone loss was 0.6% per year less in individuals classified as active at both time points than in those classified as inactive at both time points (P<.01). Similar results were observed for balance, but there was no effect of varying habitual activity on changes in muscle strength or gait velocity. There were also no differences in fracture incidence between individuals categorized as active:more active and those categorized as inactive:less active during the follow-up (adjusted hazard ratio=0.90, 95% confidence interval (CI)=0.42-1.90). This study showed that elderly men and women who maintained a habitually active lifestyle over 10 years had lower bone loss and retained better balance than those who remained habitually inactive.

Association Between Change in Bone Mineral Density and Decline in Usual Walking Speed in Elderly Community‐Dwelling Japanese Women During 2 Years of Follow‐Up

To investigate the association between change in bone mineral density (BMD) and change in usual walking speed in elderly community-living Japanese women during 2 years of follow-up. Longitudinal cohort study. Community-based. A total of 182 women aged 70 to 84 who completed a baseline survey and a follow-up survey 2 years later. An interview, anthropometric measurements, blood analysis, and physical performance tests were performed at baseline and at follow-up 2 years later. BMD was evaluated using dual-energy X-ray absorptiometry measured at the forearm. Annual percentage changes in BMD and usual walking speed during the 2-year follow-up period were calculated; annual percentage changes in BMD were summarized in quartiles. The association between annual bone loss rate and decline in usual walking speed was analyzed using multiple linear regression adjusted for changes in muscle strength, balance capability, and other potential confounders. Change in BMD was significantly related to change in usual walking speed during the 2-year follow-up. After multivariate adjustment, usual walking speed declined significantly more in elderly women whose BMD decreased (-3.5% change in walking speed in the first quartile of percentage change in BMD and -3.1% in the second quartile) than in women whose BMD increased (+1.5% in fourth quartile). Elderly women whose BMD decreased had a significantly greater decline in usual walking speed than women whose BMD increased, even after multivariate adjustment of potential confounders.

Prospective investigation of annual bone loss rate in females in Changsha city, Hunan province

To investigate prospectively the annual bone loss rate at spine, proximal femur and distal radius in females and its relationship to relevant factors. The bone mineral density (BMD) at anteroposterior lumber, proximal femur and distal radius in 220 women of Mawangdui Township, aged 36 - 60, was measured twice, March to April 2000 and March to April 2004, using a Hologic QDR 4500A fan beam X-ray bone densitometer. The annual bone loss rate was the highest during the period of 1 to 5 years since menopause, showing an annual bone loss of 1.70% at the anteroposterior spine, and 2.21%, 1.92%, and 1.56% at the femoral neck, greater trochanter, and distal radius respectively. Even before menopause bone loss was found at the femoral neck and distal radius. BMD loss at the anteroposterior spine and greater trochanter was found in the peri-menopause group. The bone loss rate was the highest in the early menopause group (1.56%/year, P < 0.01), and became lower, however, not significantly in the late menopause group (0.38%/year, P > 0.05). Age was positively correlated with the annual bone loss rates at the anteroposterior spine, greater trochanter, and distal radius (gamma = 0.223 - 0.547, P < 0.05 - 0.01), and the number of year since menopause was also positively correlated with the annual bone loss rate at anteroposterior spine and greater trochanter (gamma = 0.432 - 0.569 P < 0.05 - 0.01). However, body weight and body mass index were negatively correlated with the annual bone loss rates at the anteroposterior spine, femoral neck, and greater trochanter (gamma = 0.239 - 0.466, P < 0.05 - 0.01). Annual bone loss varies at different skeletal region. Age, years since menopause, and body weight influence the bone loss at different skeletal regions in females.

Estrogen receptor α and β polymorphisms

A cross-sectional segregation analysis of polymorphisms in the estrogen receptor (ER) genes (Pvull and Xbal in ERalpha, and Alul in ERAbeta with bone mineral density in the lumbar spine and forearm and with lipid profile was performed in 1098 postmenopausal women. Additionally, in a subpopulation of 280 women, who completed 1 year of treatment with estrogen plus progestin, the association between genotypes and the response to treatment in both plasma lipids and bone was investigated. In another untreated subpopulation of 443 women, genotype influence on the prevalence of vertebral fractures and on annual rate of bone loss during a mean follow-up period of 11 years was estimated. Baseline plasma lipids, bone mineral density, annual rate of bone loss and prevalence of spinal fractures were not significantly associated with polymorphisms in the ERbeta gene. The ERA polymorphism was significantly associated with bone loss from the distal forearm (P = 0.04) but not with bone loss from the spine. After 1 year of treatment with hormone therapy there was also a significant association between the ERbeta polymorphism and the response in total cholesterol (P = 0.02); while the ERalpha gene polymorphisms did not significantly influence the response to hormone therapy. In a large white population of postmenopausal women, ERalpha gene polymorphisms were not associated with bone mineral density or lipid profile at baseline or after hormone therapy. Conversely, the ERbeta genotype appeared to segregate with bone loss from the forearm and to modulate the decrease in total cholesterol during hormone therapy.

Which bone densitometry and which skeletal site are clinically useful for monitoring bone mass?

Long-term precision, as well as reproducibility, is important for monitoring bone mineral density (BMD) alteration in response to aging or therapy. In order to investigate which bone densitometry and which skeletal site are clinically useful for monitoring bone mass, we examined the standardized long-term precision of several bone density measurements in 83 healthy Japanese women. Annual BMD measurements were performed for 5 or 6 years using dual X-ray absorptiometry (DXA) on the lumbar spine, radius (EXP5000) and calcaneus (HeelScan); peripheral quantitative computed tomography (pQCT) on the radius (Densiscan1000); and quantitative ultrasound (QUS) on the calcaneus (Achilles+). The long-term precision error for the individual subject was given by the standard error of estimate (SEE), and the standardized long-term precision was defined as the percentage coefficient of variation (CV%) divided by the percentage ratio of the annual bone-loss rate. Based on the CV% of spinal DXA, speed of sound (SOS) and diaphyseal pQCT showed significantly higher precision than others, while radial ultradistal (UD) DXA and heel DXA showed significantly lower precision. The long-term precision errors of other measurements were statistically the same as that of the spinal DXA. The spinal DXA, the radial DXA, and pQCT at both the distal metaphysis and diaphysis showed high rates of annual bone loss. The radial trabecular BMD (pQCT) was significantly higher than that of spinal DXA. The annual rates of bone loss of QUS and of heel DXA were significantly lower than that of spinal DXA. Taken together, standardized long-term precision was obtained in the spinal DXA and radial pQCT. In conclusion, spinal DXA and radial pQCT were considered the most useful monitoring method for osteoporosis, while QUS was considered less useful.

Interaction of nutritional calcium and HRT in prevention of postmenopausal bone loss: a prospective study.

The aim of this study was to investigate the interactive effects between nutritional calcium (Ca) intake and hormone replacement therapy (HRT) on bone loss. The study population, 937 peri- and postmenopausal women, was selected from a random sample (n = 2025) of the OSTPRE-study cohort (n = 13,100) in Kuopio, Finland. Of them, 545 women had never used HRT and 392 women reported its use during the follow-up period of 6 years. Women were divided in groups according to self-reported daily nutritional Ca intake (mg/day): <648 (1st), 648-927 (2nd), >927 (3rd). Bone mineral density of the lumbar spine and femoral neck was measured with dual X-ray absorptiometry at baseline in 1989-91 and at the 5-year follow-up in 1994-97. According to analysis of variance, there were no statistically significant differences in annual bone loss rate between Ca intake tertiles in HRT never users. In HRT users the annual bone loss at the femoral neck was significantly lower in the third tertile than in the second and first tertiles. In a linear regression model, Ca intake prevented femoral bone loss in HRT users (P < 0.001) but contrast had no effect in never users. At lumbar spine, the corresponding Ca effect was weak (P = 0.063). Adjustment for potentially modifying parameters did not change these effects. In addition, HRT prevented femoral bone loss only among women with the highest Ca intake. At the lumbar spine, the difference between HRT users/non-users was significant in all tertiles but was greater in the second and third tertiles than in the first. In conclusion, nutritional Ca intake may protect HRT users from bone loss and vice versa, low nutritional calcium intake may be a risk factor for non-response to HRT.

Baseline BMD and bone loss at distal radius measured by peripheral quantitative computed tomography in peri- and postmenopausal Hong Kong Chinese women.

The current study was designed to investigate the rate of bone loss in distal radius and its association with baseline volumetric bone mineral density (BMD) and years since menopause (YSM) in peri- and postmenopausal women using precise and multislice peripheral quantitative computed tomography (pQCT; Densiscan 2000). Two hundred and five healthy Hong Kong Chinese perimenopausal ( n = 26) and postmenopausal ( n = 179) women within 10 years of the onset of menopause were recruited. Anthropometric parameters and menstrual status were also measured. The linear regression model derived from the baseline volumetric BMD revealed a significant and slightly better correlation with YSM than age, with a YSM-related annual decline of 2.56%, 1.82% and 0.65% in trabecular BMD (tBMD), integral BMD (iBMD) and cortical BMD (cBMD), respectively. Follow-up measurements after a time interval of 12 months showed that the rate of bone loss was higher than the annual decline in BMD calculated from the baseline BMD, with decreases of 2.89%, 2.16% 0.91% in tBMD, iBMD and cBMD, respectively. Baseline BMD was associated with age or YSM ( r ranges from -0.283 to -0.502; p<0.001 in all cases), but no relationship was found between annual rate of bone loss and age or YSM. The rate of bone loss did not correlate with baseline volumetric BMD values or YSM after dividing the subjects into fast bone losers (with annual tBMD loss > or =3%), normal bone losers (with annual tBMD loss > or = 1% but <3%) or slow bone losers (with annual tBMD loss <1%). The rate of bone loss was greater in both trabecular and cortical bone of postmenopausal women within the first 3 menopausal years but was only significant in the iBMD as compared with perimenopausal and postmenopausal women over 7 years after onset of menopause. The percentage distribution of slow and fast bone losers was not found to be associated with YSM. As a total of only 4 fracture cases were documented, the study could not provide conclusive information on whether perimenopausal and early postmenopausal baseline volumetric BMD or rate of bone loss determines the development of osteoporosis or fracture occurrence.

Withdrawal of hormone replacement therapy is associated with significant vertebral bone loss in postmenopausal women.

This study aimed to assess the changes in vertebral bone mineral density (BMD) after cessation of hormone replacement therapy (HRT) in postmenopausal women who had been treated on a long-term basis. Fifty healthy postmenopausal women who had been followed both during the course of HRT and after cessation of treatment in our menopause clinic were included in this study. All women had started HRT within the first 3 years after the postmenopause and had received HRT (either 1.5 mg/day of 17 beta-estradiol given percutaneously or 50 micrograms/day of 17 beta-estradiol given as a transdermal patch, combined in all women with natural progesterone or a 19-norprogesterone derivative) for a mean 5 +/- 2.4 years. In all women, vertebral BMD was assessed during the course of HRT up to the last 6 months before estrogen withdrawal, then at least once within the first 18 months after cessation of treatment. Of the initial population, 30 women were additionally reviewed later on and up to 8 years after cessation of treatment (mean duration of follow-up for the whole population: 3.9 +/- 1.7 years). Rates of changes in vertebral BMD were compared with those determined in a group of healthy untreated women who had been followed within the first years of postmenopause during the same time period as the study population. In the study group, bone loss was found to accelerate within the first 2 years after HRT withdrawal and the annual rate of loss was identical to that which occurs within the first 2 years of postmenopause in untreated women (-1.64% +/- 1.3% vs -1.52 +/- 0.9%, NS). Beyond this first 2-year time period, the annual rate of bone loss decreased as a function of time following cessation of treatment, as was observed following the menopause in untreated women (between 3 and 5 years: -0.83% + 1.35% in the study group vs -0.70% +/- 0.8% in the control group, NS). On average, 3 years after cessation of HRT mean vertebral BMD when expressed as a Z-score was significantly higher (-0.13 vs -0.89, p < 0.01) than at baseline, before HRT was started, which suggested a lasting beneficial effect on bone mass. However, even though our findings do not support the hypothesis that bone loss might continue to be accelerated several years after cessation of treatment we cannot fully address the question as to whether any residual benefit on bone mass over a longer period of time may be observed. In conclusion, the pattern of bone loss observed after cessation of estrogen therapy was found to be comparable to that which occurs in younger women within the first years after the menopause. Such a pattern needs to be kept in mind when the decision to stop HRT is taken, especially in women who were given HRT to prevent osteoporosis. The issue of assessing their risk of fracture several years after cessation of treatment thus needs to be addressed.

Effects of Lifetime Volleyball Exercise on Bone Mineral Densities in Lumbar Spine, Calcaneus and Tibia for Pre-, Peri- and Postmenopausal Women

To clarify the effects of habitual volleyball exercise on bone in women during the menopausal periods, we measured bone mineral densities (BMDs) of the lumbar spine, calcaneus and tibia every 12 months for 2 years and estimated factors related to the baseline values and annual loss rates. Forty Japanese female volleyball players 42-62 years of age, who had belonged to the district non-professional club for more than 10 years on average, were recruited. Twenty women had regular menstruation at the start, but 7 underwent menopause during the study. Fifty-nine healthy women who did not participate in habitual exercise, but were otherwise comparable with the players, were recruited as the controls. The lumbar and calcaneus BMDs were measured by dual-energy X-ray absorptiometry (DXA), and both the volumetric BMDs and cross-sectional geometry at the diaphysis of the tibia were measured by peripheral quantitative computed tomography. The baseline BMDs of all measured sites and the values of the cortical area and moment of inertia of the tibia in the players were significantly higher than the values in the control women. In the peri- and postmenopausal players, the baseline values of the lumbar and calcaneus BMDs related to total years of participating in regular exercises during adulthood including volleyball (TYE), body mass index (BMI) and years since menopause (YSM). Tibia cortical area and moment of inertia values related to TYE. Annual bone loss rates in the tibia and calcaneus of players were significantly smaller than those values in the controls. However, the bone loss rates in the lumbar spine did not differ significantly between the groups. The bone loss rate in the calcaneus was significantly related to the current number of training hours per week and YSM. The rate of bone loss in the tibia was related to BMI. These data indicated that the total number of years participating in exercise activity during adulthood have positive effects on lumbar and calcaneus BMDs and the cortical structure of the tibia. Habitual volleyball exercise apparently did not alleviate the menopause-related bone loss in the lumbar spine.

Further evaluation on long-term depot-medroxyprogesterone acetate use and bone mineral density: a longitudinal cohort study

Cross-sectional studies on the effects of depot-medroxyprogesterone acetate (DMPA) on bone mineral density (BMD) have been controversial. The present longitudinal cohort study on 59 Chinese women over a period of 3 years has shown that their annual rate of bone loss at 3 sites (0.44% in lumbar spine, 0.40% in neck of femur, 1.05% in Ward’s triangle) was substantially less than the projected values (1.1% in lumbar spine, 2.3% in neck of femur, 3.5% in Ward’s triangle) in a cross-sectional study that had demonstrated a significant reduction in BMD in DMPA users than the non-user population. The trochanter BMD measurement did not show the projected annual bone loss of 2.4%. The rate of bone loss is probably non-linear, with a rapid loss in the first 5 years and a leveling off afterwards. The duration of DMPA use was not significantly correlated with the rate of bone loss. Multiple linear regression analysis demonstrated that age and body mass index were significant variables in modeling the rate of bone loss in the lumbar spine and neck of femur, but not in the trochanter and Ward’s triangle areas. The Z scores also suggested a retardation in bone loss with time and potentially due to the effect of progesterone in decreasing bone turnover that is similar to the situation in postmenopausal women. The present data provide another aspect of reassurance to the long-term use of DMPA.

Differential effects of menopause and metabolic disease on trabecular and cortical bone assessed by peripheral quantitative computed tomography (pQCT).

The usefulness of peripheral quantitative computed tomography (pQCT) was investigated in the diagnosis of metabolic bone diseases, including osteoporosis, and especially in the different diagnostic values in trabecular and cortical components. The subjects were 460 Japanese women aged 20-86 years, including 318 healthy volunteers, 58 osteoporotics with fracture and 84 patients with diseases including amenorrhoea, steroid-induced osteoporosis, renal osteodystrophy (ROD) and primary hyperparathyroidism. Bone mineral density (BMD) was measured for more than 4 years in 74 of the healthy volunteers. BMD was measured by spinal QCT, dual X-ray absorptiometry (DXA) of the spine, radius, and heel, and pQCT of the radius and tibia. High resolution images were obtained for geometry of the radius. Radial pQCT showed a higher correlation with radial DXA than with spinal QCT, and spinal QCT showed a higher correlation with spinal DXA than with radial pQCT. The annual bone loss rates at predominantly trabecular bone sites were accelerated in both the axial and appendicular skeleton. In the fracture study, radial pQCT showed a higher odds ratio (OR = 4.4) than radial DXA, and cortical area ratio seemed to be a good predictor of fracture risk (OR = 5.2). Amenorrhoea and steroid-induced osteoporosis predominantly affected trabecular bone, ROD predominantly affected cortical bone and hyperparathyroidism affected both components, especially the cortical component. pQCT is useful for assessing both trabecular and cortical bone, to provide information on individual bone changes in metabolic bone disease and to estimate the risk of fracture.