Changes In Vertebral Bone Mineral Density Research Articles

Effect of Zoledronic Acid on Bone Mineral Density in Men with Prostate Cancer Receiving Gonadotropin-Releasing Hormone Analog

Background. Loss of bone density with androgen deprivation therapy for prostate cancer is well recognized. We assessed the effects of quarterly infusion of zoledronic acid on bone mineral density (BMD) and markers of bone turnover over a one-year period in men receiving gonadotropin-releasing hormone analog (GnRH-a) for prostate cancer. Methods. 41 subjects were randomly assigned to treatment with zoledronic acid (4 mg) IV infusion or placebo every 3 months. The primary endpoint was the change in the lumbar spine BMD after 12 months of treatment. Results. The change in vertebral BMD in the zoledronic acid group (+7.93 ± 1.4%) was significantly (P < .05) greater than the change in the placebo group (+0.82 ± 1.7%) as was the change in left femoral neck BMD (+5.05 ± 1.4% for the zoledronic acid group versus −0.48 ± 1.4% for the placebo group). The decrease in biochemical markers of bone turnover was significantly (P < .05) greater in the zoledronic acid group compared to the placebo group. Conclusion. Quarterly infusion of zoledronic acid for 1 year improved vertebral and left femoral neck BMD with a decrease in bone turnover markers in men on GnRH-a treatment. Zoledronic acid treatment appears to be promising in men with low BMD receiving GnRH-a treatment.

Long‐term effects of magnesium carbonate on coronary artery calcification and bone mineral density in hemodialysis patients: A pilot study

Observational data suggest that elevated magnesium levels in dialysis patients may prevent vascular calcification and in vitro magnesium can prevent hydroxyapatite crystal growth. However, the effects of magnesium on vascular calcification and bone mineral density have not been studied prospectively. Seven chronic hemodialysis patients participated in this open label, prospective pilot study to evaluate the effects of a magnesium-based phosphate binder on coronary artery calcification (CAC) scores and vertebral bone mineral density (V-BMD) in patients with baseline CAC scores >30. Magnesium carbonate/calcium carbonate (elemental Mg: 86 mg/elemental Ca 100 mg) was administered as the principal phosphate binder for a period of 18 months and changes in CAC and V-BMD were measured at baseline, 6, 12, and 18 months. Serum magnesium levels averaged 2.2+/-0.4 mEq/L (range: 1.3-3.9 mEq/L). Phosphorus levels (4.5+/-0.6 mg/dL) were well controlled throughout the 18 months study. Electron beam computed tomography results demonstrated a small not statically significant increase in absolute CAC scores, no significant change in median percent change, and a small none significant change in V-BMD. Magnesium may have a favorable effect on CAC. The long-term effect on bone mineral density remains unclear. Larger studies are needed to confirm these findings.

Measuring and interpreting age‐related loss of vertebral bone mineral density in a medieval population

This study investigates the age- and sex-related patterns in vertebral bone mineral density (BMD) and the relationship between BMD and vertebral osteophytosis (VO), using a specialized peripheral densitometer in a skeletal sample excavated from the British medieval village Wharram Percy. A total of 58 individuals were divided by sex into three broad age categories (18-29, 30-49, 50+ years.). Each fourth intact vertebral centra was scored for VO and 5-mm thick coronal sections scanned in a specialized peripheral densitometer (GE Lunar Piximus DXA). Changes in BMD associated with age, sex, and VO severity were examined in the whole vertebral section, a strictly trabecular region, and a primarily cortical region of bone separately. Significant change in vertebral BMD was found to occur by middle age with little or no statistical change in BMD between middle and old age. Females appear to suffer greater bone loss at an earlier age with no change in BMD between middle and old age, whereas males show a more steady loss of BMD across the age groups. The bone mineral content and BMD of the cortical region is higher in individuals with pronounced/severe osteophytosis. The unusual age- and sex-related patterns of change in vertebral BMD at Wharram Percy are compared with the patterns of age-related change from recent longitudinal population-based studies. The results emphasize the different pattern of bone loss in young adulthood seen in trabecular regions of the skeleton and highlight the importance of consideration of degenerative joint disease in BMD studies. The influence of lifestyle factors on vertebral BMD in this medieval population is also discussed.

Association of a T262C transition in exon 1 of estrogen-receptor-α gene with skeletal responsiveness to estrogen in post-menopausal women

Polymorphic genetic markers of estrogen-receptor-alpha (ERalpha) gene studied so far in osteoporosis reside in non-coding region with uncertain functional significance. The purpose of the present study was to search for nucleotides changes in the exon 1 and 5' regulatory region of ERalpha gene, to study the nature of their linkages to the previously reported Pvull polymorphism in intron 1 and their functional significance in postmenopausal osteoporosis. Direct sequencing of exon 1 and promotor region of ERalpha gene revealed a synonymous nucleotide substitution from T to C at position 262, 29 nucleotides downstream from the putative start codon. No nucleotide change was found in the promotor region. Linkage disequilibrium between the T262C polymorphism and the Pvull polymorphism in intron 1 of ERalpha gene was demonstrated in 129 post-menopausal women (p<0.001). After treating 96 post-menopausal with 0.3 mg or 0.625 mg conjugated equine estrogen (CEE) for 2 yr, vertebral bone mineral density (BMD) increased regardless of the T262C genotype. However, with regard to femoral neck BMD, only those subjects that were homozygous for the T262C polymorphism had an increase in femoral BMD (+5.9+/-1.4%, mean+/-SE; p<0.0001). Using analysis of covariance to assess the effects of the T262C polymorphism, the intronic Pvull polymorphism, doses of CEE and the corresponding baseline BMD on the changes in vertebral or femoral BMD after treatments, it was found that the change in vertebral BMD was related only to the baseline BMD (p<0.05). The change in femoral BMD was independently related to the T262C polymorphism (p<0.01) and the baseline femoral BMD (p<0.01). No effect of the Pvull polymorphism or the doses of CEE on femoral BMD was demonstrated. We concluded that the previously described intronic Pvull polymorphism of ERalpha gene is in linkage disequilibrium with a T262C polymorphism in exon 1. This T262C polymorphism appears to be more directly related to the skeletal response after long-term treatment with estrogen.

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.

Bone Mineral Density After Resumption of Menses in Amenorrheic Athletes

Amenorrheic athletes have been found to have a lower vertebral bone mineral density (BMD) than matched groups of eumenorrheic athletes. This study reports changes in BMD over a 15.5 month period in athletes who regained menses, athletes who remained amenorrheic, and athletes with regular cycles. The BMD was measured at two sites on the radius and at the lumbar vertebrae (L-1 through L-4), using single- and dual-photon densitometry, respectively. Changes in vertebral BMD were significant for the amenorrheic group (+6.3%), but not for cyclic women (-0.3%). A slight increase in radial density at S-1 and S-2 was not significant for either group. Two athletes who remained amenorrheic during this period continued to lose bone (-3.4%). We conclude that resumption of menses was the primary factor for the significant increase in the vertebral BMD of the formerly amenorrheic athletes.