Mean Change In Bone Mineral Density Research Articles

Change in Bone Mineral Density Among Adolescent Women Using and Discontinuing Depot Medroxyprogesterone Acetate Contraception

Several studies report an association between depot medroxyprogesterone acetate (DMPA) injectable contraception and decreased bone mineral density. Adolescents, who are still gaining bone, may be particularly affected, but there has been little study of the association in adolescent users and none following discontinuation. To evaluate bone mineral density changes in adolescents using and discontinuing use of DMPA contraception. A population-based prospective cohort study. One hundred seventy adolescent women, aged 14 to 18 years; 80 baseline DMPA users and 90 age-similar, unexposed comparison women. Sixty-one participants discontinued DMPA use during follow-up. Bone mineral density, measured every 6 months for 24 to 36 months at the hip, spine, and whole body, comparing mean bone mineral density changes in DMPA users and discontinuers with nonusers. Among DMPA users, bone mineral density declined significantly relative to nonusers at the hip and spine but not the whole body. Annualized mean percentage changes, adjusted for covariates, were hip, -1.81% vs -0.19%; P<.001; spine, -0.97% vs 1.32%; P<.001, and whole body, 0.73% vs 0.88%; P = .78 for DMPA users vs nonusers, respectively. New users lost bone mineral density more rapidly than prevalent users. Discontinuers experienced significantly increased bone mineral density relative to nonusers at all anatomical sites; annualized mean percentage changes were hip, 1.34% vs -0.19%; P = .004; spine, 2.86% vs 1.32%; P = .004; and whole body, 3.56% vs 0.88%; P<.001. Use of DMPA contraception in adolescents was associated with significant continuous losses of bone mineral density at the hip and spine. However, significant gains postdiscontinuation provide evidence that the loss of bone mass is apparently reversed.

Bone mineral density in patients with prostate cancer without bone metastases treated with intermittent androgen suppression

Objectives To evaluate prospectively the effects of intermittent androgen suppression (AS) on bone mineral density (BMD) in patients with prostate cancer without bone metastases. Methods A total of 19 hormone-naive patients with Stage D0 disease were treated with a luteinizing hormone-releasing hormone analog and an antiandrogen for 9 months, after which AS was discontinued. When the prostate-specific antigen level reached a predetermined threshold, AS was restarted. BMD was measured at baseline, after 9 months of AS, and at the end of the first off-treatment period or at 1 year, whichever occurred first. Results Of the 19 patients, 17 had normal BMD at baseline; 2 patients with osteopenia at baseline were excluded from the analysis. All but 1 of the 17 patients with normal baseline BMD experienced a decline in BMD in the lumbar spine or hip, or both, during AS. After 9 months, the mean BMD in these patients had decreased by 4.5% at the lumbar spine ( P = 0.0007) and by 2.5% at the hip ( P = 0.00013). After a median off-treatment period of 7.9 months, the mean change in BMD of the lumbar spine and hip relative to the post-AS values was 1.5% ( P = 0.06) and −0.01% ( P = 0.09), respectively. Conclusions The observed loss of BMD during 9 months of AS is significantly greater than the expected 0.5% to 1% annual loss. Interruption of AS attenuated the rate of bone loss, although full recovery to the baseline BMD was not achieved in all patients. These data suggest that men treated with AS should undergo baseline and periodic follow-up BMD assessments, because significant bone loss can occur during the first 9 months of AS.

Effect of a single course of isotretinoin therapy on bone mineral density in adolescent patients with severe, recalcitrant, nodular acne

BackgroundAdverse changes in bone have been reported for patients undergoing high-dose, long-term (several years) isotretinoin therapy for disorders of cornification. The effect of short-term (4-5 months) therapy at the lower dose recommended for acne on bone development in younger, growing adolescent (12-17 years) patients has not been well studied. ObjectiveThe purpose of the study was to evaluate the effect of a standard, single course of isotretinoin (Accutane) therapy on bone mineral density (BMD) of the lumbar spine and hip in adolescents ages 12 to 17 years with severe, recalcitrant, nodular acne. MethodsIn this open-label, multicenter study, 217 adolescents (81 girls) with severe, recalcitrant, nodular acne were enrolled and treated with isotretinoin twice daily with food at the recommended total dose of approximately 1 mg/kg for 16 to 20 weeks. BMD in the lumbar spine and hip was measured at baseline and at the end of therapy by dual energy radiograph absorptiometry. ResultsThere was no clinically significant mean change in BMD measured at the lumbar spine (+1.4%, range: −4.9% to +12.3%) or total hip (−0.26%, range: −11.3% to +15.0%). Hyperostosis was not observed in any patient. Typical efficacy expected in the treatment of acne was observed. ConclusionsA 16- to 20-week course of isotretinoin treatment at the recommended dose for severe acne has no clinically significant effect on lumbar spine and total hip BMD in the adolescent (12-17 years) population.

Bone mineral density in Norwegian premenopausal women

The aims of this study were: 1) to determine bone mineral density (BMD) in different age groups, 2) to determine the prevalence of low BMD, and 3) to determine the possible association between BMD and a number of risk factors in Norwegian premenopausal women. BMD of the lumbar spine (L(2)-L(4)), total body, and the hip (total femur, femur neck, and trochanter) were measured using dual-energy X-ray absorptiometry (Prodigy, Lunar) in 145 randomly selected women aged 13-39 years. Information on other factors thought to influence BMD was obtained through questionnaire and a clinical interview. The group aged 25-29 years had the highest mean BMD in the total body, lumbar spine, and total femur while the group aged 13-19 years had the highest mean BMD in the femur neck and the trochanter. The mean BMD values of Norwegian premenopausal women were 3.4-5.1% higher than US/European reference data (P<0.05). Five percent of the study sample aged 20-39 years were defined with low BMD (Z-score <-2) using the standard values from this study. Weight-bearing physical activity, body weight, body height, and age were positively associated with BMD, whilst menstrual dysfunction and previous pregnancy were associated with lower BMD in some of the measurement sites. The results show that the factors associated with BMD are extensive, and the strategies to prevent low BMD have to be multifactorial. A follow-up study should be conducted on the study sample to investigate actual mean BMD values and BMD changes through time.

Effect of zoledronic acid (ZA) versus placebo on bone mineral density (BMD) in androgen-deprived prostate cancer patients with and without bone metastases (mets)

4760 Background: Bisphosphonates can prevent BMD loss in prostate cancer patients receiving androgen deprivation. Previous studies of ZA and BMD in this population excluded patients with bone mets because of concern that mets may interfere with DEXA results. Methods: We performed a double-blind, placebo-controlled, randomized study of ZA in prostate cancer patients with and without bone mets on androgen deprivation for < 12 months. Patients were randomized to receive either 4 mg ZA or normal saline placebo IV every 3 months for 4 treatments. BMD of the femoral neck (FN) and lumbar spine (LS) were measured by DEXA at 0, 3, 6, 9, and 12 months. Results: From 1/00 through 12/02, 42 of a planned 80 patients were randomized. Accrual was stopped due to initiation of a multi-center study that is currently ongoing. BMD data are available for 18 patients who received placebo and 21 who received ZA. Baseline characteristics were well-balanced between the 2 groups (placebo vs. ZA): mean FN BMD 0.998 g/cm2 (SD 0.126) vs. 0.979 g/cm2 (SD 0.196); mean LS BMD 1.385 g/cm2 (SD 0.274) vs. 1.344 g/cm2 (SD 0.207). 9 patients in each arm had bone mets detected by bone scan. A random effect model was used to examine change in BMD over one year. The mean change in BMD per year (slope, g/cm2/year) is shown in the table below. Results are shown for all patients and for patients excluded based on bone scan abnormalities detected in the region of BMD measurement. Conclusions: When all patients were analyzed, no statistically significant difference in the mean change per year of BMD was detected. When patients with scintigraphic evidence of bone mets at the site of DEXA measurement were excluded, the expected benefit of ZA therapy became apparent. Mets detected in the region of DEXA measurement can interfere with interpretation of ZA effect. Bone marker analysis for this study is pending. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis

Depressive symptoms and bone mineral density in older men.

Most studies examining the relation between depression and bone mineral density (BMD) have been limited to psychiatric patients or to community-dwelling, older women. We conducted a cross-sectional and prospective cohort study to determine whether depressive symptoms are associated with low BMD in community-dwelling, older men. We recruited 515 men 50 years of age or older from population-based listings of age-eligible men. Participants completed the Geriatric Depression Scale (short form) and were considered depressed if they scored 6 or more out of 15 possible points. BMD was measured in the spine and hip using dual energy x-ray absorptiometry in all participants, and again an average of 3.6 years later in a random subset of 100 participants. The prevalence of depressive symptoms (GDS = 6) was 3.1% (16 of 515). We found no difference in mean BMD or mean percent change in BMD per year of the hip and lumbar spine in men who had 6 or more depressive symptoms compared with men who reported 5 or fewer symptoms of depression. These findings suggest that depressive symptoms are not associated with BMD in community-dwelling, older men.

Evaluation of Ability of Biochemical Markers of Bone Turnover to Predict a Response to Increased Doses of HRT

Antiresorptive therapy is usually given in a fixed dose, and we hypothesized that some patients receiving standard doses of hormone replacement therapy (HRT) might benefit from a higher dose, particularly if their bone turnover decreases after increasing the dose of HRT. Eighty-eight women who had been receiving standard-dose (0.625 mg/day) conjugated equine estrogens (CEE) for at least one year were randomized to take either standard-dose (0.625 mg/day, n = 36) or high-dose (1.25 mg/day, n = 52) therapy. Subjects with a uterus were allowed to take either 10 mg of medroxyprogesterone cyclically or 5 mg daily, according to personal preference. Bone Mineral Density (BMD) and biochemical markers of bone turnover were followed for 2 years. Mean bone turnover decreased significantly (-4.1% to -19.1%) after 6 months of high-dose CEE. Decreases in serum BSAP (bone-specific alkaline phosphatase) and serum or urine NTX ( N-terminal telopeptide crosslink of type I collagen) on high-dose therapy were not predictive of an improvement in BMD, but a decrease in serum CrossLaps did predict an improvement in BMD. Mean change in BMD in subjects with a significant decrease in serum CrossLaps at the anteroposterior spine was 3.1% +/- 3.9% versus 1.2% +/- 2.9% for subjects with no significant change in CrossLaps, P < 0.02. There was, however, a wide range of changes in BMD in patients with or without a significant change in CTX on high-dose HRT, making it impossible to predict an improvement in BMD based on an individual's changes in turnover. Measuring of bone density and bone turnover with better precision might be more successful in guiding individual dosing of antiresorptive therapy.

Growth hormone replacement in adults and bone mineral density: a systematic review and meta-analysis.

The effect of GH replacement on bone mineral density (BMD) in adults with GH deficiency (GHD) is uncertain. We carried out a systematic review of randomized trials that compared GH to no active treatment, with BMD as an outcome. We searched electronic databases to identify articles, abstracts and conference proceedings to March 2002. We also checked reference lists in included studies and expert reviews. Two reviewers independently extracted the data on study design and change in BMD. The results of individual trials were combined by fixed effects model meta-analysis using weighted mean difference (WMD) of change in BMD at the lumbar spine (our primary outcome) and other sites. Eighteen trials that included 700 patients met the inclusion criteria. Maximum follow-up was for 12 weeks (1 trial), 6 months (14 trials), 12 months (1 trial), 18 months (1 trial) and 24 months (1 trial). Reporting quality of both study design and results was poor. Ten trials (458 subjects) were included in the meta-analysis. We excluded those eight trials from which sufficient data could not be extracted. We found a mean change in BMD, at the lumbar spine with GH treatment, of 0.01 g/cm2 after 6 and 12 months, 0.02 g/cm2 after 18 months and 0.03 g/cm2 after 24 months. Statistical significance at the 0.05 level was just achieved at 6 and 12 months but was significant at 18 and 24 months. These changes are small and may be influenced by bias. There is evidence of a small effect of GH replacement on bone mineral density in adults with GH deficiency. The clinical importance of this is uncertain.

A prospective, randomized, placebo-controlled study of the dose effect of oral estradiol on bone mineral density in postmenopausal Chinese women

Objectives: One of the long-term consequences of estrogen deficiency in postmenopausal women is an increased risk of osteoporosis. Fractures of the hip and lumbar spine are associated with considerable morbidity and mortality. Estrogen replacement therapy reduces the risk of osteoporosis, but there is no clear agreement on the most appropriate doses to be used. The aim of this study was to compare changes in bone mineral density (BMD) measurements using conventional and lower dose estradiol. Methods: A prospective, randomized, placebo-controlled 12-month study of the effect of 1 and 2 mg estradiol on BMD in 152 hysterectomized postmenopausal Chinese women with no contraindication to the use of estrogen replacement therapy. Results: Over 12 months, spinal BMD in placebo treated patients decreased by a mean of 2% from baseline (−0.02±0.03 g/cm 2) while it increased by 2% in the 1 mg (0.02±0.03 g/cm 2) and 3% in the 2 mg group (0.03±0.03 g/cm 2). Mean changes in BMD over 12 months in the hip were −0.02±0.02 g/cm 2 (−2%), 0.01±0.02 g/cm 2 (+1%) and 0.01±0.03 g/cm 2 (+1%) in the placebo, 1 and 2 mg estradiol groups, respectively ( P<0.05). Relative to placebo, increases in BMD in both 1 and 2 mg groups were statistically significant for both spine and hip ( P<0.05). However, there was no significant difference in the increase in BMD between the 1 and 2 mg doses for either lumbar spine or hip ( P=0.82, 0.53, respectively). Conclusion: The results of our study show that a 1 mg dose of oral estradiol is effective in preventing bone loss in postmenopausal Chinese women.

Changes in Bone Density and Turnover Explain the Reductions in Incidence of Nonvertebral Fractures that Occur during Treatment with Antiresorptive Agents

Some, but not all, antiresorptive agents have been shown to reduce the risk of nonvertebral fractures. Agents that significantly reduced nonvertebral fracture risk also appear to produce larger mean increases in bone mineral density (BMD) and reductions in biochemical markers (BCM) of bone turnover, compared with other agents. To examine the extent to which increases in BMD and reductions in BCM during antiresorptive therapy are associated with reductions in risk of nonvertebral fractures, we performed a meta-analysis of all randomized, placebo-controlled trials of antiresorptive agents conducted in postmenopausal women with osteoporosis (i.e. prior vertebral fracture or low BMD) with available relevant data. A total of 18 such trials with usable data were identified, including a total of 2,415 women with incident nonvertebral fractures over 69,369 women-years of follow-up. Poisson regression was used to estimate the association between changes in BMD or BCM during the first year and overall reductions in risk of nonvertebral fractures (vs. the placebo group) across all trials. Larger increases in BMD and larger reductions in BCM were significantly associated with greater reductions in nonvertebral fracture risk. For example, each 1% increase in spine BMD at 1 yr was associated with an 8% reduction in nonvertebral fracture risk (P = 0.02). Mean BMD changes at the hip were smaller than at the spine, but the predicted net effect on fracture risk was the same; an agent that increases spine BMD by 6% at 1 yr reduces nonvertebral fracture risk by about 39%, and an agent that increases hip BMD by 3% at 1 yr reduces nonvertebral fracture risk by about 46%. The results also predict that a 70% reduction in resorption BCM would reduce risk by 40%, and a 50% reduction in formation BCM would reduce risk by 44%. It appears that either BMD or BCM changes are able to explain the effect of treatment, because a separate variable for treatment was not independently significant in any models. These data demonstrate that larger increases in BMD at both the spine and hip and larger reductions in both formation and resorption BCM are associated with greater reductions in the risk of nonvertebral fractures. Antiresorptive agents that do not produce large increases in BMD or large reductions in BCM do not appear to and would not be expected to decrease the risk of nonvertebral fractures.

The effect of femhrt® and Prempro™ on bone mineral density as assessed by response to treatment.

Objective: The impact of hormone replacement therapy (HRT) on bone mineral density (BMD) is usually assessed by comparing groups for mean BMD changes. The probability of an individual patient’s response to HRT is more difficult to determine, but becomes an important factor as different estrogen and progestin components comprise HRT. We compared the number of patients responding to two different HRT treatments or placebo (calcium only) to determine differences between treatments and among skeletal sites with respect to the number of patients maintaining BMD at the lumbar spine, femur, and total body.

Comparison of Alendronate and Intranasal Calcitonin for Treatment of Osteoporosis in Postmenopausal Women

Both alendronate and calcitonin, the latter administered intranasally, reportedly increase bone mineral density (BMD) and reduce bone turnover, but alendronate seems to be somewhat more effective. This study directly and prospectively compared these treatments in 299 women with an average age of 64 years who were at least 5 years postmenopausal. BMD was monitored at the lumbar spine and femoral neck and trochanter by dual-energy x-ray absorptiometry during 12 months of treatment with 10 mg of alendronate, a matching placebo, or open-label intranasal calcitonin in a daily dose of 200 IU. Serum bone-specific alkaline phosphatase (BSAP) and urinary N-telopeptide of type I collagen adjusted for urinary creatinine (NTx) were measured as markers of bone formation and resorption, respectively. BMD at both the lumbar spine and trochanter increased significantly more in patients given alendronate than in those given calcitonin (Fig. 1). The effect of alendronate significantly exceeded that in placebo patients at all sites. Both serum BSAP and urinary NTx decreased substantially more in alendronate-treated patients than in those given calcitonin or placebo at all intervals (Fig. 2). Adverse events in general and serious complications were noted in similar proportions of all groups. Effects on the upper gastrointestinal tract were more prevalent with alendronate therapy than with calcitonin therapy but were nearly as frequent in patients given the alendronate placebo. Findings in this double-blind randomized study indicate that alendronate was more effective than intranasal calcitonin in promoting increased BMD in postmenopausal women. It suppressed bone turnover more than did calcitonin during 1 year of treatment.Fig. 1: BMD. Mean percent change (±SE) in BMD of the lumbar spine, hip trochanter, and femoral neck with 10 mg of alendronate (ALN, ○), 200 IU of intranasal calcitonin (CT, ▵), and placebo tablet (PBO, □) over 12 months. P values for between-group comparisons are presented.Fig. 2: Biochemical markers of bone turnover. Mean percent change from baseline and SE in BSAP and NTx with 10 mg of alendronate (ALN, ○), 200 IU of intranasal calcitonin (CT, ▵), and placebo tablet (PBO, □) over 12 months. P values for between-group comparisons are presented.J Clin Endocrinol Metab 2000;85:1783–1788

Prevention of early postmenopausal bone loss with cyclical etidronate

Cyclical etidronate has been shown to be effective in the treatment of established postmenopausal osteoporosis but less is known about its effects on early menopausal bone loss. The aim of the study was to establish the effects of cyclic etidronate therapy on spinal and proximal femoral bone mineral loss in early postmenopausal women. One hundred and seven women who were within 6 months to 3 years of the menopause were recruited into a 2-year, randomised, placebo-controlled, double-blind trial. Spinal bone mineral density was within 2 SD of the age-matched mean reference value at baseline. Bone mineral density in the lumbar spine and proximal femur was assessed by dual energy X-ray absorptiometry at baseline and thereafter at 6 monthly intervals for 2 years. Urinary collagen cross-links (deoxypyridinoline and pyridinoline) were measured at the same time points. Seventy-seven women completed the study. At the end of the treatment period, the mean bone mineral density change from baseline in the treated group was +0.14% and -0.06% in the lumbar spine and femoral neck, respectively, compared to -1.49 and -2.22 in the control group. Overall, there was a significant difference between the two groups at both these sites (p=0.01 and 0.001, respectively). No significant differences between the groups were demonstrated at the greater trochanter or Ward's triangle. The conclusion was that cyclical etidronate therapy prevents bone loss in the spine and femoral neck in early postmenopausal women. It provides a safe and effective therapeutic option for the prevention of postmenopausal osteoporosis in women who are unwilling or unable to tolerate hormone replacement therapy.

Comparison of different treatment modalities for postmenopausal patients with osteopenia: hormone replacement therapy, calcitonin and clodronate

Objective To evaluate the effectiveness of hormone replacement therapy (HRT), clodronate, calcitonin and a clodronate plus calcitonin combination in postmenopausal patients with osteopenia.Methods One hundred postmenopausal patients with osteopenia, with bone mineral density (BMD) measurements at least one standard deviation below the mean value for young premenopausal subjects (T score <-1), were studied. They had no contraindications to HRT, clodronate or calcitonin use and were randomized to four different treatment groups. Patients in group I were treated with transdermal estradiol 50 μg/day and oral medroxyprogesterone acetate 10 mg/day during the last 12 days of the month; group II received oral clodronate 400 mg/day for 1 month out of every 3 months; group III received calcitonin nasal spray 100 IU/day; and patients in group IV were treated with oral clodronate 400 mg/day for 1 month out of every 3 months plus calcitonin nasal spray 100 IU/day. Elementary calcium 1000 mg/day was supplemented to patients in all groups. Spinal and femoral neck BMD measurements and markers of bone mineral metabolism were measured in each patient before treatment and 6, 12 and 18 months after treatment in 86 patients.Results Significant increases in mean lumbar spine BMD were found in the group receiving HRT, and at the end of 18 months there was a 2.69 ± 0.76% increase, compared with baseline. Mean femoral neck BMD also increased by 2.22 ± 0.57% in the HRT group; this was significantly different from baseline, resulting in a higher bone mass gain than in the other three groups. Increases in both lumbar spine and femoral neck BMD were found in patients treated with clodronate, although the only significant increase was observed in lumbar spine BMD at the end of 18 months. The mean changes in BMD were not significantly different, compared with the other groups, and at the end of 18 months there was a 2.20 ± 0.58% increase at the lumbar spine. The mean vertebral and femoral neck BMD did not change significantly throughout the study period in patients receiving calcitonin. At the end of 18 months, there was a 0.13 ± 0.52% decrease and a 0.11 ± 0.49% increase in mean lumbar spine and femoral neck BMD, respectively, compared with baseline. The combination of clodronate plus calcitonin increased mean lumbar spine and femoral neck BMD by 2.08 ± 1.05% and 1.46 ± 1.09%, respectively, at the end of 18 months, but these increases were not significantly different from those in the groups where these agents were used alone. Significant decreases in bone resorption and in markers of bone formation were observed in all groups.Conclusion HRT was found to be the most effective treatment regimen in postmenopausal patients with osteopenia, compared with clodronate, calcitonin and a clodronate plus calcitonin combination. Clodronate or calcitonin might be alternatives when HRT is contraindicated or refused by the patient, although calcitonin was found to be less effective. The clodronate plus calcitonin combination was not superior to either of these agents when used alone.

Bone mineral density 6 years after a hip fracture: a prospective, longitudinal study

The purpose of this prospective study was to extend the results of previous studies to determine if an accelerated rate of loss of bone mineral density (BMD) continues for 6 years after a hip fracture. Eighty-five elderly patients who had sustained a hip fracture had determinations of BMD made at the time of fracture; 55 of these patients were available for reassessment of BMD 1 year later, and 21 were available for reassessment of BMD 6 to 7 years later. The change in BMD from injury to 1 year and from 1 to 6 years was determined and correlated with pre- and postinjury variables, such as ambulatory ability, dietary intake of calcium, serum vitamin D levels, and mental status. There was a marked decrease in BMD in the in the first year after fracture, with the mean change in BMD being −4.3% at the femoral neck and −1.8% at the lumbar spine. Between 1 and 6 years after fracture, however, there was a dramatic increase in the BMD at both the femoral neck and lumbar spine measurement sites. Relative to 1 year after fracture, the mean increases were 7.7% at the femoral neck and 4.5% at the lumbar spine. In many cases, the loss of bone mineral that occurred in the first year after fracture was completely recouped in the subsequent 5 years. Five of the 21 patients (24%) sustained a contralateral hip fracture in the 6 years after the index fracture. Lumbar spine BMD was lower at baseline ( p = 0.02), 1 year after fracture ( p = 0.007), and 6 years after fracture ( p = 0.003) in patients who sustained a second hip fracture than in those who did not. There was a general decrease in the functional activity level of patients in the 6 years after a hip fracture, but there were no statistically significant relationships between changes in BMD and the functional mobility of patients. The mean calcium intake in patients improved remarkably in the 6 years after fracture, but there was no correlation between daily calcium intake and changes in BMD. During the first year after a hip fracture, there is a rapid loss of bone mineral from the lumbar spine and contralateral femoral neck. Between 1 and 6 years after fracture, however, BMD is likely to increase, perhaps to levels greater than those at baseline. Although this investigation is small, the findings of this study point to the importance of further larger studies to further clarify the natural history of BMD after a hip fracture and the potential impact of pharmacological intervention on that natural history.

Allelic variation at the interleukin-1 receptor antagonist gene is associated with early postmenopausal bone loss at the spine

Genetic factors play an important role in determining bone mineral density (BMD) in later life, with the genetic influence mediated through effects on both peak mass and on age- and menopause-related bone loss. At menopause there is an increase in the production and activity of various cytokines and growth factors within the bone microenvironment. The activity of interleukin-1 (IL-1), a powerful stimulant of osteoclastic bone resorption, is increased in estrogen-deficient states with increased production of IL-1 and inhibition of the IL-1 receptor antagonist (IL-1ra). Treatment with IL-1ra blocks the bone loss associated with ovariectomy in animals and the IL-1 receptor antagonist gene (IL-1RN) is therefore a potential candidate gene for the regulation of postmenopausal bone loss. We examined the relationship between annual rates of change in BMD over 5 years and an 86 bp variable number tandem-repeat polymorphism of the IL-1RN gene in 108 early postmenopausal women. All women were within 5 years of a natural menopause at the study’s onset, healthy, and not on hormone replacement therapy or other medication known to affect bone metabolism. BMD was measured annually over the 5 year study period at the lumbar spine and femoral neck using dual-energy X-ray absorptiometry. Three alleles were identified (A1 = 4 repeats, A2 = 2 repeats, A3 = 5 repeats), with five genotypes observed: A1A1 (41.7%), A1A2 (45.4%), A2A2 (6.5%), A1A3 (2.8%), and A2A3 (3.7%). For analysis, alleles were collapsed into a biallelic system grouping the A1 and A3 alleles. There was no significant relationship between the IL-1RN genotypes and baseline bone mass at either the spine or hip. IL-1RN genotype was significantly associated with annual rates of change in spinal bone mass ( p < 0.05), and this finding remained significant after adjustment for age, weight, and baseline BMD. Carriage of at least one copy of the A2 allele was associated with reduced bone loss at the spine (mean change in BMD ± SD: −0.81 ± 1.46%/year) when compared with noncarriage of the A2 allele (mean change −1.38 ± 1.48%/year), p = 0.05. We therefore conclude that allelic variation at the IL-1RN locus is associated with differential rates of early postmenopausal bone loss at the spine. Further research will be required to clarify the mechanisms underlying these findings and to determine whether this association translates into a significant long-term effect on BMD and fracture in later life.

A prospective study of bone mineral density change in Taiwan.

In 1989, a cross-sectional study was carried out in Lin-Kou Township, Taiwan, to determine the distribution of bone mineral density (BMD) in the lumbar spine of Chinese people. Lumbar spine BMD was measured using dual-photon absorptiometry in 404 healthy volunteers (266 women and 138 men, aged 15 to 83 years). In 1994-1995, 318 of the same volunteers were reexamined for the present study. Except for there being fewer males and smokers present, there were no significant differences between the second survey respondents and nonrespondents. Spine BMD decreased at over 1% per year in Chinese women over age 50, which was somewhat higher than reported for caucasian women. Since there was a loss of BMD in Chinese women after their 20s, a case can be made for starting preventive activities for female adolescents. There were no differences in the mean BMD change rates among the different age groups of Chinese men. Baseline BMD, menopause, and weight change were associated with the lumbar spine BMD change rates in Chinese women. Body mass index was the only variable significantly associated with BMD change in Chinese men. The rate of BMD change was not associated with diet.

Effects of anteversion on femoral bone mineral density and geometry measured by dual energy X-ray absorptiometry: A cadaver study

The effect of femoral neck anteversion on bone mineral density (BMD) and geometry as measured by dual energy X-ray absorptiometry (DXA) was assessed using 64 right proximal femora from 36 male and 28 female cadavers. The anteversion angle was measured on computed tomography (CT) images, and DXA measurements were made both in the neutral position (i.e., at 0° anteversion, femoral neck axis parallel to the table) and in the simulated anteverted position (i.e., femoral shaft axis parallel to the table, greater and lesser trochanters in contact with the table, and femoral neck free). The mean anteversion angle measured by CT was 19.3° (range 6°–38°). Anteversion was associated with a significant elevation in femoral neck BMD of +2.8% (range −5.3%–+9.8%) ( p < 0.05), and the femoral neck BMD increased with increasing anteversion ( p < 0.01). Trochanteric BMD was less affected by anteversion, with an average increase of only 0.2% (range −5%–5.9%) ( p = n.s.) in the anteverted position, but there was a significant positive association between the change in trochanteric BMD and the anteversion angle ( p < 0.01). Anteversion produced a mean reduction of −2.4% (range −7.6%–+4.3%) ( p < 0.001) in apparent femoral neck axis length, while femoral neck width remained generally unaffected. These data confirm that femoral BMD as measured by DXA is affected by femoral anteversion with a lesser magnitude than previously reported. The use of trochanteric BMD may minimize the influence of anteversion. While the mean changes in BMD and neck axis length attributable to anteversion are modest, the considerable interindividual variability in the magnitude of the effects demonstrates that other factors, such as, the complex geometry of femoral neck modifies the effect of anteversion on BMD measurements. The error in BMD introduced femoral anteversion may represent a significant confounding influence in cross-sectional and longitudinal studies. Careful repositioning of the foot and leg is essential in monitoring changes in BMD longitudinally. Knowledge of the effects of femoral anteversion may assist in understanding the relation of femoral BMD and neck axis length to hip fracture.

Alendronate treatment of the postmenopausal osteoporotic woman: Effect of multiple dosages on bone mass and bone remodeling

The effects of the aminobisphosphonate alendronate sodium on bone mass and markers of bone remodeling were investigated. In a multicenter, randomized, double-blind, placebo-controlled, 2-year study, 188 postmenopausal women, aged 42 to 75 years, with low bone mineral density (BMD) of the lumbar spine were randomly assigned to 1 of 6 daily treatment groups: placebo for 2 years, alendronate 5 or 10 mg for 2 years, alendronate 20 or 40 mg for 1 year followed by placebo for 1 year, or alendronate 40 mg for 3 months followed by 2.5 mg for 21 months. All subjects were given 500 mg/d of elemental calcium as calcium carbonate. At each dose, alendronate produced significant reductions in markers of bone resorption and formation, and significantly increased bone mass at the lumbar spine, hip, and total body, as compared with decreases (significant at lumbar spine) in subjects receiving placebo. In the 10-mg group, mean urinary deoxypyridinoline/creatinine had declined by 47% at 3 months, and mean serum osteocalcin by 53% at 6 months. Mean changes in BMD over 24 months with 10 mg alendronate were +7.21% +/- 0.49% for the lumbar spine, +5.27% +/- 0.70% for total hip, and +2.53% +/- 0.68% for total body (each P < 0.01) compared to changes of -1.35% +/- 0.61%, -1.20% +/- 0.64% and -0.31% +/- 0.44% at these sites, respectively, with placebo treatment. Progressive increases in BMD of both lumbar spine and total hip were observed in the second year of treatment with 10 mg alendronate (both P < 0.05). Alendronate, a potent inhibitor of bone resorption, reduces markers of bone remodeling and significantly increases BMD at the lumbar spine, hip, and total body, and is well tolerated at therapeutic doses (5 or 10 mg daily) in the treatment of osteoporosis in postmenopausal women.

Effect of ipriflavone on bone mineral content in osteoporotic patients

Although numerous studies have demonstrated that ipriflavone prevents bone loss, its effect on bone mass remains to be quantitatively assessed by dual-energy x-ray absorptiometry (DXA), a recently developed diagnostic technique which enables precise measurement of bone mineral density (BMD). In this study, we investigated the effect of ipriflavone on BMD in female outpatients with osteoporosis by means of DXA and single-photon absorptiometry (SPA). The study group consisted of 23 female patients with postmenopausal or senile osteoporosis (age: 50–80 years, mean 62.4 years; body weight: 39–63 kg, mean 49.2 kg; height: 145–163 cm, mean 150.8 cm). Nineteen untreated female outpatients (age: 61–65 years) served as a control group. BMD of L1-4 in both the study and control groups was measured by DXA before and after 1 year of treatment with and without ipriflavone (600 mg/day per os), but only 19 of the study group patients were evaluated for BMD by SPA at the radius. For DXA, the mean BMD in the study group was 0.651 g/cm2 before ipriflavone treatment and 0.647 g/cm2 after treatment, with a mean percent change in BMD of 99.5%. For SPA, the mean BMD was 0.495 g/cm2 before ipriflavone treatment and 0.504 g/cm2 after treatment, with a mean percent change in BMD of 101.6%. For patients in the study group aged 61–65 years (n=9), the mean percent change in BMD by DXA after 1 year of treatment was 101.6%. In contrast, the mean percent change in BMD for the control patients of the same age bracket (n=19) was 96.5%. The results by DXA confirmed that ipriflavone inhibits loss of bone mass, making it a useful agent for the treatment of postmenopausal and senile osteoporosis.