High prevalence of spine–femur bone mineral density discordance and comparison of vertebral fracture risk assessment using femoral neck and lumbar spine bone density in Korean patients

The aim of this study was to evaluate the prevalence of spine–femur discordance, and to compare the effectiveness of femoral neck (FN) and lumbar spine (LS) bone mineral density (BMD) for estimation of the risk of vertebral fractures. Women who were evaluated with dual energy X-ray absorptiometry between January 2001 and December 2005 were enrolled in this study. Vertebral fracture risk was calculated using initial FN and LS BMD. The follow-up vertebral X-rays from all subjects were reviewed, and the calculated estimated risk using the Fracture Risk Assessment Tool (FRAX^®) was compared with the actual prevalence of vertebral fractures during the follow-up period. Among a total of 443 women with a mean age of 58.5 years, 130 women (29.3 %) demonstrated femur–spine discordance (i.e., a difference between FN and LS BMD of >1 SD). Most subjects having discordance showed lower LS BMD (73.1 %) compared to FN BMD. During the mean 7-year follow-up period, 12 (2.7 %) vertebral fractures occurred. In cases with high estimated fracture risk (>20 % for estimated fracture risk), using LS BMD significantly reflected the actual vertebral fracture in total subjects [odds ratio (OR) 19.29, 95 % confidence interval (CI) 4.21–88.46], in subjects with spine–femur discordance (OR 16.00, 95 % CI 1.91–134.16), and in subjects with spine–femur discordance having lower LS BMD (OR 20.67, 95 % CI 1.63–262.71). In comparison, the estimated risk using FN BMD did not reflect the actual occurrence of vertebral fractures. In conclusion, a significant number of Korean subjects exhibited spine–femur discordance, and LS BMD might be more appropriate for estimation of vertebral fracture risk.     

The effect of high-dose vitamin D on bone mineral density and bone turnover markers in postmenopausal women with low bone mass—a randomized controlled 1-year trial

Summary  

Vitamin D is widely used in osteoporosis treatment, although the optimal dose is not known. This 1-year clinical study among 297 women aged 50–80 years old showed that a vitamin D₃ dose of 6,500 IU/day was not better than the standard dose of 800 IU/day in improving bone mineral density (BMD) in the hip and spine.     

Degenerative changes at the lumbar spine—implications for bone mineral density measurement in elderly women

Summary

Degenerative changes of the lumbar spine may lead to misinterpretation of bone mineral density (BMD) measurements and cause underdiagnosis of osteoporosis. This longitudinal study of 1,044 women, 75 years at inclusion and followed for 10 years, shows that identification of apparent degenerative changes on the dual energy X-ray absorptiometry (DXA) scan can increase the proportion diagnosed.

Introduction

In the elderly, degenerative manifestations in the lumbar spine may result in falsely elevated BMD values, consequently missing a large proportion of those with osteoporosis. Our aim was to determine the distribution and impact of degenerative changes on lumbar spine DXA over time and its clinical implications.

Methods

Participants were 1,044 women from the population-based Osteoporosis Risk Assessment cohort. All women were 75 years old at invitation and followed up after 5 years (n?=?715) and 10 years (n?=?382). Degenerative changes were evaluated visually on the DXA image for each vertebra L1 to L4 (intraobserver precision kappa values of 0.66–0.70).

Results

At baseline, apparent degenerative changes were more frequent in the inferior segments of the lumbar spine [5 % (L1), 15 % (L2), 26 % (L3), and 36 % (L4)] and increased over time. At 10 years, the prevalences were 20 % (L1), 39 % (L2), 59 % (L3), 72 % (L4), resulting in a significant increase in overall BMD. In women without apparent degenerative changes, BMD remained stable between 75 and 85 rather than an expected bone loss. At baseline, 37 % had osteoporosis (BMD?<??2.5) at L1–L4; exclusion of women with apparent degenerative changes increased this proportion to 47 %. Using L1–L2, which was less prone to degenerative changes, 46 % of women were classified as osteoporotic regardless of degenerative changes.

Conclusion

Degenerative changes were very common in elderly women, accelerated disproportionately over time, were increasingly frequent from vertebrae L1 to L4, and had significant impact on diagnosing osteoporosis. This suggests that routine reporting of spine BMD at L1–L2 would add valuable information for reassessment and monitoring.     

HDL cholesterol and bone mineral density: is there a genetic link?

Overwhelming evidence has linked cardiovascular disease and osteoporosis, but the shared root cause of these two diseases of the elderly remains unknown. Low levels of high density lipoprotein cholesterol (HDL) and bone mineral density (BMD) are risk factors for cardiovascular disease and osteoporosis respectively. A number of correlation studies have attempted to determine if there is a relationship between serum HDL and BMD but these studies are confounded by a number of variables including age, diet, genetic background, gender and hormonal status. Collectively, these data suggest that there is a relationship between these two phenotypes, but that the nature of this relationship is context specific. Studies in mice plainly demonstrate that genetic loci for BMD and HDL co-map and transgenic mouse models have been used to show that a single gene can affect both serum HDL and BMD. Work completed to date has demonstrated that HDL can interact directly with both osteoblasts and osteoclasts, but no direct evidence links bone back to the regulation of HDL levels. Understanding the genetic relationship between BMD and HDL has huge implications for understanding the clinical relationship between CVD and osteoporosis and for the development of safe treatment options for both diseases.     

Pressure-induced pain on the tibia: an indicator of low bone mineral density?

Previous literature investigating bone pain in osteoporosis has prominently focused on painful conditions following osteoporotic fractures. “Is osteoporosis really a silent disease without bone pain and tenderness unless a fracture occurs?” Our aim in this study was to answer the question by assessing the questionable tenderness on tibia bones of fracture-free patients with low bone density and to compare the findings with a normal population. One-hundred-thirty-three consecutive postmenopausal female patients with the mean age of 56 years admitted to our clinic for bone mass measurement were included in the study. Bone mineral density (BMD) values of lumbar spine (L2–L4) and right proximal femur (neck, trochanter, Ward’s triangle) were measured by dual-energy X-ray absorptiometry (DXA). Patients with T scores lower than ?1 formed the osteopenic-osteoporotic group of patients (low BMD group) whereas those with T scores higher than ?1 constituted the normal BMD group according to the osteoporosis definition regarding T score for DXA. Mechanical pressure was applied by a hand algometer on the middle points of three equally divided sections on the anterior part of tibia, and the pressure levels starting the pain sensation (POPL) were recorded. Although the patients in the normal BMD group reported consistently high POPL at all regions of tibia for all BMD measurement sites, this difference reached to a statistical significance level only for the femur neck region. Only mean POPL for the whole tibia had independent association with only femur neck BMD by multiple linear regression analysis. These results are encouraging for assessing the significance of pressure-induced tibial pain as an indicator of low BMD in the future.     

Is a change in bone mineral density a sensitive and specific surrogate of anti-fracture efficacy?

Anti-resorptive agents perturb steady state remodeling; they suppress, but do not abolish, the birth rate of new basic multicellular units (BMUs). In doing so, remodeling goes to completion with bone formation in the many BMUs created before treatment but now with fewer resorption cavities appearing concurrently. As a result, cortical porosity and trabecular stress concentrators decrease reducing bone fragility. From this improved bone strength, steady state is re-established at a slower remodeling rate that again produces bone fragility but more slowly as fewer new BMUs, each with a less negative BMU balance, produce cortical thinning and porosity, trabecular thinning and loss of connectivity while bone fragility progresses rapidly in controls. Thus, the fracture risk reduction--the incidence of fractures in patients treated with an anti-resorptive agent relative to the incidence in controls--is the net effect of the slowing or partial reversal of fragility and then reduced progression of structural abnormalities in treated patients and continued structural decay in controls. Although some morphological features in treated patients and controls may be captured in the bone mineral density (BMD) measurement, many are not. The early increase in BMD is largely determined by the pre-treatment remodeling rate whereas the later and more modest BMD increase is a function of the degree of suppression of remodeling and secondary mineralization. When pre-treatment remodeling rate is low, the increase in BMD is small but the fracture risk reduction (relative to controls with comparable baseline characteristics) is no different to that in patients with high baseline remodeling (relative to their controls) and a greater BMD increase. Therefore, a small increase in BMD does not mean treatment has failed and a large increase in BMD is not indicative of a greater fracture risk reduction.     

The efficacy and tolerability of once-weekly alendronate 70 mg on bone mineral density and bone turnover markers in postmenopausal Chinese women with osteoporosis

Osteoporosis has become an important health problem in postmenopausal Chinese women. Bisphosphonates currently are the preferred therapy for treating osteoporosis. However, the use of daily regimen of alendronate in women at risk for osteoporosis has been relatively low in China because of its dosing inconvenience. To determine the efficacy and tolerability of once-weekly alendronate 70 mg in Chinese, a multicenter, randomized, double blind, placebo controlled study was performed in China. Five hundred and sixty postmenopausal women (≤85 years old) with osteoporosis were randomly assigned to receive either alendronate 70 mg or placebo once-weekly for 12 months. All women received calcium 500 mg daily and vitamin D 200 IU daily. A significant increase in lumbar spine BMD was already evident at 6 months of alendronate treatment (P < 0.001). The alendronate group showed significant increase (P < 0.001) in BMD at 12 months at both the spine and hip when compared with the placebo group (lumbar spine 4.87% vs. 0.4%, femoral neck 2.47% vs. 0.31%, trochanter 3.24% vs. 0.78%, total hip 2.56% vs. 0.28%, respectively). The percentage of women with ≥0% and ≥3% BMD increase in lumbar spine was significantly greater in women with alendronate than placebo (P < 0.001). Significant reduction in urine N-telopeptide (NTx) and serum bone-specific alkaline phosphatase were evident at 6 and 12 months, respectively, with alendronate treatment. No significant differences in the incidence of adverse experiences and upper gastrointestinal adverse experiences were seen. We conclude that once-weekly alendronate 70 mg is an effective and well-tolerated agent for the treatment of postmenopausal osteoporosis in Chinese women.     

Long-term effects on bone mineral density and bone metabolism of 6 months’ treatment with gonadotropin-releasing hormone analogues in Japanese women: comparison of buserelin acetate with leuprolide acetate

Our objective was to assess the effects of 6 months’ treatment with two types of gonadotropin-releasing hormone (GnRH) analogues on lumbar bone mineral density (BMD) and bone metabolism. We studied 27 women who had been given a diagnosis of endometriosis or uterine myoma. The subjects received drug therapy for 6 months and were subsequently followed up for 1 year. The BMD of the lumbar spine (L2, L3, L4) was measured by dual energy X-ray absorptiometry four times: at baseline, after 6 months, after 12 months, and after 18 months. The serum concentrations of sex steroids and bone metabolic markers were measured at the same times as BMD. Compared with the baseline value, the mean decrease in the buserelin group L2–4 BMD was 3.7% at 6 months, 1.7% at 12 months, and 0.4% at 18 months. In the leuprolide group, L2–4 BMD decreased respectively by 5.1%, 6.2%, and 4.3%. Serum concentrations of calcium increased significantly after 6 months of treatment (P < 0.05) and returned to the baseline level at 12 months in both groups. In the leuprolide group, the intact osteocalcin concentration after 6 months was significantly higher than the baseline value, and after 12 months, it decreased to the baseline level. Our results indicate that the effect on BMD of 6 months’ treatment with GnRH analogues virtually resolves by 1 year after treatment, provided that drugs affecting bone metabolism are not given during this period.     

Total body,lumbar spine and hip bone mineral density in overweight adolescent girls: decreased or increased?

Despite the epidemic of overweight adolescents, the effect of being overweight on bone mineral density (BMD) during this period is poorly understood. However, recent studies have suggested that overweight adolescents have lower BMD compared to normal-weighted adolescents after adjusting for body weight. The aim of this study was to determine the influence of being overweight on bone status in a group of adolescent girls. This study included 22 overweight (BMI >25 kg/m2) adolescent girls (15.4 ± 2.4 years old) and 20 maturation-matched (15.2 ± 1.9 years old) controls (BMI <25 kg/m2). Bone mineral area, bone mineral content, BMD at the whole body (WB), lumbar spine (L2–L4), femoral neck (FN), total hip (TH) and body composition (lean mass and fat mass) were assessed by dual-energy X-ray absorptiometry (DXA). Calculation of the bone mineral apparent density (BMAD) was completed for the WB and for L2–L4. Expressed as crude values, DXA measurements of BMD at all bone sites (TB, L2–L4, TH and FN) were higher in overweight adolescent girls compared to controls. After adjusting for either body weight, lean mass or fat mass, these differences disappeared. Finally, BMAD of the L2–L4 remained higher in overweight girls compared to controls after adjusting for lean mass. We conclude that overweight adolescent girls do not have lower BMD when compared with controls, even when BMD values are adjusted for weight, lean mass or fat mass.     

Low bone mineral density in the femoral neck of medieval women: a result of multiparity?

An archaeological investigation of a medieval cemetery gave us the opportunity to investigate 49 Danish skeletons dating from 1000 to 1250 A.D. and to compare them with 298 contemporary Danes (aged 19-79 years) and assess the millennial trend in bone mineral density (BMD) in populations considered genetically closely related. BMD and bone mineral apparent density (BMAD) of the femoral neck were measured by dual-energy X-ray absorptiometry (DEXA) and transformed into z scores. BMD(zscore) was significantly lower in medieval women (-0.54 +/- 0.25, p = 0.04), whereas BMD(zscore) in medieval men was significantly higher (0.55 +/- 0.22, p = 0.02). In medieval women, BMD(zscore) tended to increase with age (r = 0.42, p = 0.07), whereas no change was seen in men (r = 0.19, not significant [n.s.]). Also, BMAD(zscore) was significantly elevated in medieval men (1.00 +/- 0.28, p < 0.01), but in medieval women no difference was found (-0.28 +/- 0.21, n.s.). However, the correlation between BMAD(zscore) and age was significant in the medieval women where it increased with advancing age (r = 0.49, p = 0.03). In conclusion, medieval women had lower BMD when compared with contemporary women, but this relationship was reversed in women who survived to older ages. In contrast, medieval men had significantly higher BMD as compared with contemporary men at all ages. The observed lower BMD in medieval women can be explained by the well-known selective mortality among the younger women. A high birth rate and prolonged periods of lactation are the main reasons for the observed increased mortality, and therefore can also very likely explain the associated low BMD. The increase in the incidence of osteoporosis in modern elderly women could possibly, or partially, be explained by the survival of women who would have died prematurely had they lived in earlier centuries.     

Effects of a multi-component exercise program and calcium–vitamin-D3-fortified milk on bone mineral density in older men: a randomised controlled trial

Summary  We examined the independent and combined effects of a multi-component exercise program and calcium–vitamin-D₃-fortified milk on bone mineral density (BMD) in older men. Exercise resulted in a 1.8% net gain in femoral neck BMD, but additional calcium–vitamin D₃ did not enhance the response in this group of older well-nourished men. Introduction  This 12-month randomised controlled trial assessed whether calcium–vitamin-D₃-fortified milk could enhance the effects of a multi-component exercise program on BMD in older men. Methods  Men (n = 180) aged 50–79 years were randomised into: (1) exercise + fortified milk; (2) exercise; (3) fortified milk; or (4) controls. Exercise consisted of high intensity progressive resistance training with weight-bearing impact exercise. Men assigned to fortified milk consumed 400 mL/day of low fat milk providing an additional 1,000 mg/day calcium and 800 IU/day vitamin D₃. Femoral neck (FN), total hip, lumbar spine and trochanter BMD and body composition (DXA), muscle strength 25-hydroxyvitamin D and parathyroid hormone (PTH) were assessed. Results  There were no exercise-by-fortified milk interactions at any skeletal site. Exercise resulted in a 1.8% net gain in FN BMD relative to no-exercise (p < 0.001); lean mass (0.6 kg, p < 0.05) and muscle strength (20–52%, p < 0.001) also increased in response to exercise. For lumbar spine BMD, there was a net 1.4–1.5% increase in all treatment groups relative to controls (all p < 0.01). There were no main effects of fortified milk at any skeletal site. Conclusion  A multi-component community-based exercise program was effective for increasing FN BMD in older men, but additional calcium–vitamin D₃ did not enhance the osteogenic response.     

Dose–response study of denosumab on bone mineral density and bone turnover markers in Japanese postmenopausal women with osteoporosis

Summary  

The efficacy and safety of denosumab were evaluated in Japanese postmenopausal women with osteoporosis. Total hip and distal 1/3 radius bone mineral densities (BMDs) were increased, and lumbar spine BMD was increased in magnitude with increasing dose. Bone turnover markers significantly decreased compared with placebo. Denosumab was well tolerated in Japanese subjects.     

The prevalence of significant left–right hip bone mineral density differences among black and white women

Summary  

In a cross-sectional retrospective study, we examined the prevalence of significant opposite hip bone mineral density difference among white and black women. Left–right hip bone mineral density difference was a common finding in both races, raising the possibility that osteoporosis can be missed if only one hip is imaged.     

Serum sclerostin levels positively correlate with lumbar spinal bone mineral density in postmenopausal women—the six-month effect of risedronate and teriparatide

Summary  

Sclerostin is expressed by osteocytes and inhibits bone formation by osteoblasts. In this study, serum sclerostin was positively correlated with either lumbar spinal bone mineral density or T-score. Furthermore, serum sclerostin was increased after 6 months treatment with risedronate, whereas remained unchanged after 6 months teriparatide treatment.     

The effect of exercise on pQCT parameters of bone structure and strength in postmenopausal women—a systematic review and meta-analysis of randomized controlled trials

Summary  

Inconsistent study findings of exercise on areal bone density highlight the need to include parameters of bone geometry and volumetric bone density measurements. Using a systematic review and meta-analysis, we found a decrease in bone loss through the maintenance of cortical and trabecular volumetric bone mineral density (BMD). Studies with longer exercise durations and larger sample sizes are needed.     

Calcium supplementation and weight bearing physical activity--do they have a combined effect on the bone density of pre-pubertal children?

The adaptation of bone to exercise has been shown to be modified by dietary calcium intake. The aim of this randomised controlled trial was to investigate whether there was a differential response to calcium supplementation in elite gymnasts and school children controls. The primary hypothesis was that gymnasts who took calcium supplements would have greater increases in cortical and trabecular volumetric bone mineral density (vBMD) at the radius and tibia. Secondary outcomes studied were changes in bone geometry at the radius and tibia and lumbar spine and whole body measurements. Children were randomised to 12 months daily supplementation of 500 mg elemental calcium (1250 mg (in the form of calcium carbonate salt)) or placebo. Outcome measures were assessed using peripheral quantitative computed tomography (pQCT) (distal and diaphyseal radius and tibia) and dual energy X-ray absorptiometry (DXA) (lumbar spine and whole body). Eighty-six subjects participated in the trial (44 gymnasts, 42 controls) and 75 subjects completed the trial (39 gymnasts, 36 controls). Data were analysed by analysis of covariance adjusting for baseline value of bone parameters, age, height, gender and puberty, and delay between baseline measurement and start of intervention. The primary analysis was for a calcium-exercise interaction; a pooled calcium effect with no interaction was also tested. Results are presented as ratios (95% confidence intervals). At the distal tibia, trabecular vBMD showed a significant interaction (p=0.04), with controls (1.00: 0.99, 1.09) responding more than gymnasts (0.98: 0.94, 1.02) to supplementation. At the distal radius, change in trabecular vBMD was not significant (p=0.05). There were no differences in change in cortical vBMD at either site between the gymnasts and controls (tibia: p=0.82, radius: p=0.88). For all other secondary outcomes at radius, tibia, spine and whole body no significant interactions were found. In conclusion, there was no beneficial effect of additional calcium in gymnasts who already consume their recommended nutrient intake (888 mg/day; United Kingdom reference nutrient intake for 8- to 11-year-olds is 555-800 mg/day) for calcium. We speculate that gymnasts have already adapted their bones (geometry and vBMD) to the demands imposed upon them by the loading they are subjected to during gymnastics and do not benefit from additional calcium supplementation.     

Acrylic bone—cement: Influence of mixer design and unmixed powder

The effects of hand mixing with two different mechanical mixing systems (fixed versus rotating central axis) on unmixed powder content, macroporosity, density, and bending strength of acrylic bone—cement are compared. The effects of voids and unmixed powder on cement bending strength are also evaluated. In acrylic cement, both unmixed powder monomer and voids 1 mm and larger can be easily visualized and analyzed on radiographs of 3-mm-thick samples. Image analysis allowed demonstration of a significant increase in unmixed powder content (P < .0001), in cement prepared using a vacuum mixing system with a fixed central axis compared with both the rotating axis system and hand mixing. The rotating-axis system produced cement of higher density compared with hand mixing only (P = .004). There was a significant correlation between the number of voids measured per square centimeter and cement bending strength (P < .0001), as well as an independent and significant correlation between unmixed powder content and cement bending strength (P < .0001). Mechanical mixing using a fixed central axis produced significantly weaker cement compared with both hand mixing (P < .015) and the rotating-central-axis system (P < .0001). A 15% drop in strength between the two mechanical mixing systems was observed. It is therefore concluded that the use of different rotating systems in mechanical mixers can influence void and unmixed powder content and, consequently, the mechanical properties of acrylic cement, and that unmixed powder is an independent factor affecting the bending strength of the cement.     

Dual X-ray absorptiometry (DXA) of the lumbar spine in a clinical paediatric setting: does the method of size-adjustment matter?

Dual X-ray absorptiometry (DXA) is increasingly used in a clinical setting to evaluate bone mass in children. Areal Bone Mineral Density (aBMD) measurements are known to be influenced by body size, but there is no consensus on the optimal way to deal with this for individual patients. AIM: To compare parameters of bone mass with varying degrees of size correction and to determine the effect on the categorisation of patients as normal or abnormal. SUBJECTS AND METHODS: Healthy children (n = 78) and 4 groups of patients (n = 194) underwent DXA scans of the lumbar spine (L2-4, GE Lunar Prodigy). Five measures of bone mass were derived, all adjusted for age and sex: aBMD, BMAD (BMC/BA (1.5)), BMCh (BMC/height3), BMCa (BMC adjusted for BA), BMCt (BMC adjusted for BA and height). SD scores were calculated for each parameter for patients using data from healthy controls. RESULTS: Compared to healthy children, all patient groups had significantly reduced BMD SD scores (P < 0.001). Mean BMAD, BMCa and BMCt SD scores were significantly lower in only 2/4 patient groups, whilst BMCh SD scores were low only in one group. BMCt showed no advantage over BMCa. The proportion of patients with SD scores <-2 was 27% for aBMD but between 10-13% for BMAD, BMCh and BMCa. CONCLUSIONS: All size-corrected parameters of bone mass performed similarly and classified significantly fewer patients as abnormal than did aBMD. The use of one of these parameters should reduce the number of patients diagnosed inappropriately with 'low bone mass'. However, without validation against an outcome measure or 'gold standard' of bone density or structure, it is not possible to determine which parameter is most correct.