Initial BMD Research Articles

Radiological Factors Associated with Bisphosphonate Treatment Failure and Their Impact on Fracture Healing in Postmenopausal Women with Osteoporotic Vertebral Fractures.

(1) Background: Bisphosphonate treatment failure is one of the most difficult clinical problems for patients with osteoporosis. This study aimed to analyze the incidence of bisphosphonate treatment failure, associated radiological factors, and effect of fracture healing in postmenopausal women with osteoporotic vertebral fractures (OVFs). (2) Methods: A total of 300 postmenopausal patients with OVFs who were prescribed bisphosphonate were retrospectively analyzed and divided into two groups according to the treatment response: response (n = 116) and non-response (n = 184) groups. The radiological factors and the morphological patterns of OVFs were included in this study. (3) Results: The initial BMD values of the spine and femur in the non-response group were significantly lower than those in the response group (all Ps < 0.001). The initial BMD value of the spine (odd ratio = 1.962) and the fracture risk assessment tool (FRAX) hip (odd ratio = 1.32) showed statistical significance in logistic regression analysis, respectively (all Ps < 0.001). (4) Conclusions: The bisphosphonate non-responder group showed a greater decrease in BMD over time than the responder group. The initial BMD value of the spine and the FRAX hip could be considered radiological factors influencing bisphosphonate non-response in the postmenopausal patients with OVFs. The failure of bisphosphonate treatment for osteoporosis has a possible negative on the fracture healing process in OVFs.

Radiomorphometric Indicators, their Reliability in Detecting Early Signs of Osteoporosis in Menopausal Women

Background: The aim of this study was to evaluate the diagnostic value of panoramic radiography and the radiomorphometric indices in osteoporosis identification. Methods and Results: The research included 60 women (average age of 62,907,07 years) in the postmenopausal stage who were subjected to an assessment of bone density through the DEXA test and were divided into 2 groups based on the value of the DEXA test from the lumbar region (L1-L4): Main group (MG) included 30 women with osteoporosis (T-score&lt;-2.5) and Comparison group (CG) included 30 women without osteoporosis (T-score&gt;-2.5). Panoramic radiography were used to assess the mandibular cortical index (MCI), mental index (MI), panoramic mandibular index (PMI) Based on the porosity level, Klemetti et al.(1994) has categorized MCI into three categories (C1, C2, and C3). MCI–C1, which represents the normal appearance of the lower jaw cortex without changes in bone quality, was found only in CG in 63.33%. MCI-C2 and MCI-C3 were found in 70% and 30% of cases, respectively, in MG. In CG, MCI-C2 was found in 36.67% of cases and MCI-C3 in 0% of cases. There was a significant difference between the two study groups in the distribution of MCI (P=0.000). MI below 3 mm was found in 19(63.33%) of cases in CG and 27(90.00%) in MG (OR=5.211, 95% CI: 1.278-21.237, P=0.0213). PMI below 0.3mm was found in 7(23.33%) of cases in CG and 19(63.33%) in MG (OR=5.675 95% CI: 1.841-17.494, P=0.0025). MCI sensitivity and specificity for osteoporosis were 70% (95% CI: 50.60%-85.27%) and 63.33% (95% CI: 43.86%-80.07%), respectively; PPV, NPV, and accuracy were 65.62% (95% CI: 53.03%-76.35%), 67.86% (95% CI: 53.41%-79.54%) and 66.67% (95% CI: 53.31%-78.31%), respectively. MI sensitivity and specificity at a cutoff point of 3 mm for osteoporosis were 90% (95% CI: 73.47%-97.89%) and 36.67% (95% CI: 19.93%-56.14%), respectively; PPV, NPV, and diagnostic accuracy were 58.70% (95% CI: 51.35%-65.67%), 78.57% (95% CI: 53.18%-92.21%) and 63.33% (95% CI: 49.90%-75.41%), respectively. PMI sensitivity and specificity at a cutoff point of 0.3 mm for osteoporosis were 63.33% (95% CI: 43.86%-80.07%) and 76.67% (95% CI: 57.72%-90.07%), respectively; PPV, NPV, and diagnostic accuracy were 73.08% (95% CI: 57.32%-84.58%), 67.65% (95% CI: 55.66%-77.69%) and 70.00% (95% CI: 56.79%-81.15%), respectively. Conclusion: PR can be a useful tool to identify early signs of osteoporosis by using the evaluation of radiomorphometric indices. MCI, MI, and PMI can be potential screening tools for initial BMD loss.

Hearing and Balance Exceed Initial Bone Mineral Density in Predicting Incident Fractures: A 25-Year Prospective Observational Study in Menopausal Women With Osteoporosis.

ABSTRACTHearing and balance deteriorate, and fracture incidence increases with age, especially in women. The aim of the present study was to investigate whether impaired hearing and body balance are stronger predictors of fractures than bone mass. Between 1995 and 1997, 80 women, aged 50 to 70 years, with primary osteoporosis, taking menopausal hormone therapy, mainly for menopausal symptoms, participated in a double‐blind, randomized, placebo‐controlled study of treatment with growth hormone versus placebo. All women received calcium 750 mg and vitamin D 400 U daily. They were then examined yearly until 2007 and followed up by registers until 2020. Hearing was assessed by audiometry. Body balance and fine motor function were tested according to the Bruininks‐Oseretsky test. Bone properties were measured with DXA. Data on fractures were derived from the Gothenburg Hospital register. Over the 25‐year follow‐up, 50 women (63%) sustained 104 fractures, most often related to accidental falls. Thoracic and lumbar spine fractures were most common (36%). Other fractures occurred in the pelvis (14%), humerus (14%), hip (11%), and wrist (10%). Hearing impairment at baseline, measured as pure tone average‐high (p = 0.007), pure tone average‐mid (p = 0.003), and speech‐recognition score (p = 0.025), was associated with a subsequent first fracture, as were worse body balance (p = 0.004), upper limb coordination (p = 0.044), and higher running‐speed agility (p = 0.012). After adjustment for age and BMD, pure tone average‐high (p = 0.036), pure tone average‐mid (p = 0.028), and body balance (p = 0.039) were still significantly associated with incident fractures. Bone mineral content, BMD, and treatment at baseline were not associated with subsequent fracture. In conclusion, hearing and body balance at baseline exceeded initial BMD in predicting incident fractures in osteoporotic women regardless of treatment during 25‐year follow‐up. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Targeted bone density testing for optimizing fracture prevention in Canada.

This analysis was performed to inform initial BMD testing as part of Osteoporosis Canada's Guidelines Update for women and men at average risk, assuming a pharmacotherapy intervention threshold of 20% for FRAX® MOF computed with BMD. Women and men age 50 + without previous low-trauma fracture or high-risk medication use were identified in a BMD registry for the province of Manitoba, Canada. Fracture probability assessments with the Canadian FRAX® tool were computed without and with BMD (denoted MOF-clinical and MOF-BMD, respectively). The study population consisted of 50,700 women (mean age 65.5 ± 9.4years) and 4152 men (69.2 ± 10.0years). FRAX MOF-clinical score was > 10% in 33.8% of women and 13.3% of men (P < 0.001). The median (interquartile range [IQR]) age for MOF-clinical to reach 10% in women was 70 (69-72) and 65years (62-67) years in the absence and presence of additional FRAX clinical risk factors, respectively. In men, comparable ages were 83years [82-86] and 76 [70-78] years. Using MOF-BMD of 20% as the intervention threshold, 4.3% of women and 0.7% of men qualified for treatment. MOF-clinical > 10% had high sensitivity to identify those qualifying for treatment (99.3% in women and 99.1% in men). An age-based rule ("BMD testing is indicated at age 70 if no additional FRAX clinical risk factors are present, or at age 65 if one or more clinical risk factors exists") gave similarly high sensitivity (women 99.9% and men > 99.9%). FRAX without BMD offers an effective strategy to identify individuals meeting the current Canadian treatment threshold based upon FRAX® with BMD (≥ 20%). Moreover, this can be operationalized using simple age cutoffs of 70years in the absence of additional clinical risk factors and 65years in the presence of additional clinical risk factors.

Zoledronic Acid Cut Older Men's Fractures

Zoledronic Acid Cut Older Men's Fractures

The impact of osteoporosis (as measured by lumbar spine quantitative computed tomography) on disease activity and survival in myeloma patients: A 13‐year prospective study

Myeloma is a progressive neoplastic disease characterized by plasma cell dyscrasia, progressive bone loss, and pathological fractures. We conducted a prospective, single center study on myeloma patients to determine the impact of osteoporosis on disease activity and survival. Data collected on 108 patients followed for 13 years included clinical demographics, markers of myeloma activity, skeletal radiography, and bone densitometry. There were 56 men and 52 women with mean age of 69 years. Of these, 78% presented with stage I/II disease, 11% underwent stem cell or bone marrow transplants, 78% received adjuvant intravenous bisphosphonates, and 80% died during the course of the study (median survival of 47.3 months). There were 66% with osteoporosis, 54% with fractures, and 56% with lytic bone lesions. Femoral neck dual energy X-ray absorptiometry (DXA) and lumbar spine quantitative computed tomography (QCT) were major independent predictors of patient survival. Kaplan-Meier survival estimates demonstrated that patients presenting with a lumbar spine QCT T-score ≤ -3.5, died on average 18 months earlier than those with a lumbar spine QCT T-score > -3.5. These data suggest that the severity of osteoporosis, as defined by initial BMD T-score values, significantly impact on patient survival.

Teriparatide Reduces Bone Microdamage Accumulation in Postmenopausal Women Previously Treated With Alendronate

Suppression of bone turnover by bisphosphonates is associated with increased bone microdamage accumulation in animal models. Our objective was to study the effects of teriparatide treatment on changes in microdamage accumulation at the iliac crest in previously treatment-naïve patients or in those switched from alendronate to teriparatide. Sixty-six postmenopausal women with osteoporosis (mean age, 68.0 yr; and mean BMD T-score of -2.8 at lumbar spine and -1.7 at total hip; 62% with prevalent fractures) entered this prospective, nonrandomized study and started with 24-mo 20 microg/d subcutaneous teriparatide treatment in monotherapy: 38 patients stopped previous alendronate treatment (10 mg/d or 70 mg/wk for a mean duration of 63.6 mo) and switched to teriparatide, whereas 28 were previously treatment naïve. Thirty-one paired biopsies with two intact cortices were collected and analyzed for microstructure and microdamage accumulation at baseline and after 24 mo of teriparatide administration. After 24 mo of teriparatide treatment, crack density (Cr.Dn), crack surface density (Cr.S.Dn), and crack length (Cr.Le) were decreased in previously alendronate-treated patients, whereas only Cr.Le was reduced in former treatment-naïve patients. Patients with lower initial femoral neck BMD also showed a higher reduction of microdamage accumulation. Better bone microarchitecture correlated positively, whereas bone turnover markers and age did not correlate with reduced microdamage accumulation on teriparatide. In conclusion, teriparatide reduces microdamage accumulation in the iliac crest of patients previously treated with alendronate. There is insufficient evidence to suggest that age or bone turnover would be associated with this change.

C89 Hormone naive patients with advanced prostate cancer have lower initial BMD than healthy controls

C89 Hormone naive patients with advanced prostate cancer have lower initial BMD than healthy controls

Ghrelin and Bone: Is There an Association in Older Adults?: The Rancho Bernardo Study

Laboratory studies suggest that ghrelin is involved in bone metabolism, but studies of ghrelin and bone in humans are limited. We studied sex-specific associations of ghrelin with BMD, NTX, and bone loss. Ghrelin was not associated with BMD or bone loss in either sex. There was a significant inverse association with NTX in men but not in women. Ghrelin is a gastric hormone recently shown to be associated with bone metabolism in animal and in vitro studies. Studies in humans are limited. We investigated the association of ghrelin with BMD, the bone resorption marker N-telopeptide (NTX), and bone loss in older men and women. Participants were 977 community-dwelling men and non-estrogen-using postmenopausal women, 50-91 years of age. Plasma ghrelin was measured by radioimmunoassay from blood obtained between 1984 and 1987. Between 1988 and 1991, BMD was measured at the midshaft radius by single photon absorptiometry and at the femoral neck, total hip, and lumbar spine by DXA. Axial BMD measurements were repeated an average of 4 years later in 544 participants. Bone turnover was assessed by NTX in urine obtained at the same time as the initial BMD. Multiple regression analyses were used to test sex-specific associations of ghrelin with BMD, NTX, and bone loss in both sexes. No significant ghrelin-BMD or ghrelin-bone loss associations were observed in either sex, after adjusting for age and body mass index (BMI). Ghrelin was inversely associated with NTX in men and positively associated with NTX in women, independent of age. After adjusting for both age and BMI, this association reached statistical significance in men and was weakened in women. Ghrelin may be associated with bone turnover, but there is no evidence for an association with BMD or short-term change in BMD in older adults.

Vertebral Fracture Risk Reduction With Strontium Ranelate in Women With Postmenopausal Osteoporosis Is Independent of Baseline Risk Factors

Strontium ranelate (2 g/day) was studied in 5082 postmenopausal women. A reduction in incident vertebral fracture risk by 40% was shown after 3 years. This effect was independent of age, initial BMD, and prevalent vertebral fractures. Strontium ranelate is an orally active treatment able to decrease the risk of vertebral and hip fractures in osteoporotic postmenopausal women. The aim of this study was to assess the efficacy of strontium ranelate according to the main determinants of vertebral fracture risk: age, baseline BMD, prevalent fractures, family history of osteoporosis, baseline BMI, and addiction to smoking. We pooled data of two large multinational randomized double-blind studies with a population of 5082 (2536 receiving strontium ranelate 2 g/day and 2546 receiving a placebo), 74 years of age on average, and a 3-year follow-up. An intention-to-treat principle was used, as well as a Cox model for comparison and relative risks. The treatment decreased the risk of both vertebral (relative risk [RR] = 0.60 [0.53-0.69] p < 0.001) and nonvertebral (RR = 0.85 [0.74-0.99] p = 0.03) fractures. The decrease in risk of vertebral fractures was 37% (p = 0.003) in women <70 years, 42% (p < 0.001) for those 70-80 years of age, and 32% (p = 0.013) for those > or = 80 years. The RR of vertebral fracture was 0.28 (0.07-0.99) in osteopenic and 0.61 (0.53-0.70) in osteoporotic women, and baseline BMD was not a determinant of efficacy. The incidence of vertebral fractures in the placebo group increased with the number of prevalent vertebral fractures, but this was not a determinant of the effect of strontium ranelate. In 2605 patients, the risk of experiencing a first vertebral fracture was reduced by 48% (p < 0.001). The risk of experiencing a second vertebral fracture was reduced by 45% (p < 0.001; 1100 patients). Moreover, the risk of experiencing more than two vertebral fractures was reduced by 33% (p < 0.001; 1365 patients). Family history of osteoporosis, baseline BMI, and addiction to smoking were not determinants of efficacy. This study shows that a 3-year treatment with strontium ranelate leads to antivertebral fracture efficacy in postmenopausal women independently of baseline osteoporotic risk factors.

Association of endothelial nitric oxide synthase genotypes with bone mineral density, bone loss, hip structure, and risk of fracture in older women: The SOF study

Nitric oxide (NO) is an important bone-signaling molecule. We examined the associations between the Glu298Asp polymorphism of NOS3, indices of bone strength, and the incidence of fracture among 6691 women aged 65 years and older enrolled in the Study of Osteoporotic Fractures. Calcaneal BMD was measured at an initial exam and after an average of 5.9 years of follow-up. Hip BMD was measured at an initial exam and after 3.7 years of follow-up. Baseline spine BMD and hip structural parameters were measured. Incident hip fractures were confirmed by review of radiographic reports; follow-up was greater than 98% complete. Incident vertebral fractures were defined by morphometry using lateral spine radiography at baseline and an average of 3.7 years later. The frequencies of the NOS3 Glu298Asp genotypes were Glu/Glu = 46.2%, Glu/Asp = 42.7%, and Asp/Asp = 11.1%. There were no significant associations between NOS3 genotypes and initial calcaneal BMD, hip BMD, or rate of change in hip or calcaneal BMD. None of the hip structural parameters differed substantially by genotype. NOS3 genotype was not significantly associated with either incident or prevalent radiographic vertebral fractures. Women with the heterozygous Glu/Asp genotype had a borderline statistically significantly lower rate of hip fracture than either the Glu/Glu genotype (HR = 0.87, 95% CI: 0.74, 1.01) or the Asp/Asp genotype (HR = 0.78, 95% CI: 0.62, 0.98). In conclusion, the Glu298Asp polymorphism does not contribute substantially or consistently to indices of bone strength in this sample of older white women, although our findings suggest allelic variation at the NOS3 locus maybe associated with hip fracture risk. Confirmation of these findings is needed in other populations and with additional markers within and flanking the NOS3 gene region.

Multiple Genetic Loci From CAST/EiJ Chromosome 1 Affect vBMD Either Positively or Negatively in a C57BL/6J Background

Skeletal phenotype analyses of 10 B6.CAST-1 congenic sublines of mice have revealed evidence for the presence of three closely linked QTLs in Chr 1 that influence femoral vBMD both positively and negatively. BMD is an important component of bone strength and a recognized predictor of risk for osteoporotic fracture. Our goal in this study was to fine map the chromosomal location of volumetric BMD (vBMD) quantitative trait loci (QTLs) in mouse distal chromosome 1 (Chr 1). After several backcrosses of the B6.CAST-1T congenic strain, which carried the initial BMD QTL in Chr 1 with B6 mice, the N10F1 generation mice were intercrossed to obtain recombinations that yielded different regions of the QTL. Thirty-eight polymorphic markers were used to fine map the initial 1T QTL region (100-192 Mb). Different skeletal parameters were compared between the 10 sublines and B6 female mice at 16 weeks of age. A t-test was used to determine the significant difference between sublines and B6 control mice, whereas one-way ANOVA and posthoc (Newman-Keuls) tests were performed to compare the phenotype between the sublines. Significantly higher femur vBMD was found in sublines that carried cast alleles from 100 to 169 and 172 to 185 Mb of the centromere compared with the B6 control mice (10-12%, p < 0.001). However, sublines that carried cast alleles from 185 to 192 Mb showed significantly lower femur vBMD compared with the control mice (-6%, p < 0.05). Furthermore, femur vBMD phenotype showed a negative correlation with endosteal circumference (r = -0.8, p = 0.003), and a strong correlation with cortical thickness for combined data from the 10 sublines (r = 0.97, p < 0.001). Moreover, a high correlation was found between body weight and both periosteal and endosteal circumferences for sublines carrying cast alleles from 167 to 175, 168 to 185, and 169 to 185 Mb, whereas no significant correlation was found between these parameters for sublines carrying cast alleles from 172 to 185 Mb. Genetic analysis using congenic sublines revealed that the initial BMD QTL on Chr 1 is a complex site with multiple loci affecting bone phenotypes, showing the value of the congenic approach in clearly identifying loci that control specific traits.

Predictive Value of BMD for Hip and Other Fractures

The relationship between BMD and fracture risk was estimated in a meta-analysis of data from 12 cohort studies of approximately 39,000 men and women. Low hip BMD was an important predictor of fracture risk. The prediction of hip fracture with hip BMD also depended on age and z score. The aim of this study was to quantify the relationship between BMD and fracture risk and examine the effect of age, sex, time since measurement, and initial BMD value. We studied 9891 men and 29,082 women from 12 cohorts comprising EVOS/EPOS, EPIDOS, OFELY, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, DOES, Hiroshima, and 2 cohorts from Gothenburg. Cohorts were followed for up to 16.3 years and a total of 168,366 person-years. The effect of BMD on fracture risk was examined using a Poisson model in each cohort and each sex separately. Results of the different studies were then merged using weighted coefficients. BMD measurement at the femoral neck with DXA was a strong predictor of hip fractures both in men and women with a similar predictive ability. At the age of 65 years, risk ratio increased by 2.94 (95% CI = 2.02-4.27) in men and by 2.88 (95% CI = 2.31-3.59) in women for each SD decrease in BMD. However, the effect was dependent on age, with a significantly higher gradient of risk at age 50 years than at age 80 years. Although the gradient of hip fracture risk decreased with age, the absolute risk still rose markedly with age. For any fracture and for any osteoporotic fracture, the gradient of risk was lower than for hip fractures. At the age of 65 years, the risk of osteoporotic fractures increased in men by 1.41 per SD decrease in BMD (95% CI = 1.33-1.51) and in women by 1.38 per SD (95% CI = 1.28-1.48). In contrast with hip fracture risk, the gradient of risk increased with age. For the prediction of any osteoporotic fracture (and any fracture), there was a higher gradient of risk the lower the BMD. At a z score of -4 SD, the risk gradient was 2.10 per SD (95% CI = 1.63-2.71) and at a z score of -1 SD, the risk was 1.73 per SD (95% CI = 1.59-1.89) in men and women combined. A similar but less pronounced and nonsignificant effect was observed for hip fractures. Data for ultrasound and peripheral measurements were available from three cohorts. The predictive ability of these devices was somewhat less than that of DXA measurements at the femoral neck by age, sex, and BMD value. We conclude that BMD is a risk factor for fracture of substantial importance and is similar in both sexes. Its validation on an international basis permits its use in case finding strategies. Its use should, however, take account of the variations in predictive value with age and BMD.

Association of the G-174C variant in the interleukin-6 promoter region with bone loss and fracture risk in older women.

We analyzed the association between the IL-6 G-174C polymorphism and osteoporosis phenotypes in 3376 older women. Women with the C/C genotype had a significantly slower rate of decline in hip BMD and a 33% lower risk of wrist fracture than women with the G/G genotype. Variation at the IL-6 locus may contribute to the genetic susceptibility to bone fragility. Interleukin 6 (IL-6) promotes osteoclast formation and bone resorption. The C allele of the G-174C polymorphism in the IL-6 promoter region has been related to lower gene transcription and plasma IL-6 levels. In this study, we evaluated the relationship between the IL-6 G-174C polymorphism and BMD, the rate of decline in BMD, and the risk of fracture in 3376 women 65 years of age and older participating in the Study of Osteoporotic Fractures. BMD was measured at the distal and proximal radius using single photon absorptiometry and at the hip using DXA. Hip BMD was measured again an average of 3.5 years later. Incident fractures over an average of 10.8 years of follow-up were confirmed by physician adjudication of radiology reports. Distal and proximal radius BMD was lowest among women with the G/G genotype, intermediate in the heterozygotes, and highest in women with the C/C genotype (p = 0.016 and p = 0.049, respectively), although the differences between the genotypes were small. While there were no differences by genotype with initial hip BMD, women with the C/C genotype experienced a slower rate of decline in total hip and femoral neck BMD compared with women with the G/G genotype (p = 0.004 and p = 0.029, respectively). Women with the C/C genotype also had 33% lower risk of wrist fracture compared with women with the G/G genotype, independent of age, body mass index, estrogen use, and study center (RR, 0.67; 95% CI, 0.45, 1.00; p = 0.048), whereas heterozygous women had a more intermediate risk (RR, 0.85; 95% CI, 0.65, 1.12; p = 0.256). No association was found between genotype and risk of hip or all non-spine fractures. These results suggest that the IL-6 G-174C promoter polymorphism may be a genetic marker for bone loss and wrist fracture among older women.

Zinc status and bone mineralisation in adolescent girls

The aim of the project was to assess the relationship between zinc status and bone mineralisation in pre-menarcheal adolescent girls. One hundred and thirty-nine healthy pre-menarcheal girls (Tanner pubic hair stage ⩽4), aged 12.4±1.0 years, had two visits at an interval of 2 years. Serum and urine zinc concentrations (Zn S; Zn U; Zn U/ creatinine), insulin-like growth factor 1 (IGF-I), and markers of bone turn-over, i.e. osteocalcin and parathormone (PTH), concentrations were measured at the first visit. Lumbar (L2–L4) bone mineral content and density (BMC, BMD) were measured at both visits. BMC and BMD and their increase at the follow-up after 2 years were compared with biochemical data by multiple regression. The stage of puberty was added as a covariable in the analysis. At the first visit, a significant correlation was found between sexual maturity and initial BMC, BMD, height, weight, and IGF-I. Zn S was negatively correlated with osteocalcin. Zn U showed a positive correlation with BMC, BMD, IGF-I, height, weight, and PTH. At the second visit, sexual maturity showed a positive correlation with BMD and weight increments and a negative one with BMC and height gains. Zn S was significantly related with BMD increase. These correlations suggest that zinc plays a role in normal growth and bone mineralisation during puberty onset.

IMPACT OF SUBJECTS?? INITIAL CHARACTERISTICS AND EXERCISE TYPE INTERVENTION ON BMD CHANGES IN POSTMENOPAUSAL WOMEN

Despite a reduced skeletal response to mechanical stimulus, older women present a greater skeletal response variability when compared with young women. PURPOSE This study was designed to determine the influence of subject's individual characteristics and exercise type on bone mineral density change (ΔBMD) in the femoral neck and lumbar spine. METHODS Subjects were 36 women, 53–78 yrs, at least 1 yr postmenopausal, not taking any medication affecting bone. Subjects were randomly assigned to a hydro-gymnastics (HG, n = 20) and step aerobics (SG, n = 16) groups during 18 months, 2 or 3 sessions/wk, respectively. Ground reaction forces of SG program were between 1.6–1.7 of body weight. Assessment of BMD, fat mass and fat-free mass was performed with DXA. Upper and lower body muscle strength was evaluated with a hand dynamometer and an isometric leg press test. Calcium and magnesium on the plasma were measured by atomic absorption spectrophotometry. Calcium and magnesium intake were evaluated with 3-d food records. Stepwise regression was used to analyze the contribution of initial subjects characteristics on ΔBMD. Predictors selected by regression were then used as covariates to analyze group differences on ΔBMD. RESULTS Age explained 16.4% of the ΔBMD variance on femoral neck (β = 0.405, p = 0.021). Initial lumbar spine BMD (β = −0.367, p = 0.028) and fat-free mass (β = −0.351, p = 0.035) explained 27.3% of the ΔBMD variance on spine. Using these predictors as covariates, ANCOVA showed ΔBMD group differences on spine (HG 2.8 ± 0.6% vs. SG 0.4 ± 0.8%, p < 0.001) but not on femoral neck (HG −0.7 ± 0.9% vs. SG – 0.6 ± 1.0%, p = 0.801). CONCLUSION The efficacy magnitude of a specific exercise intervention for bone seems to be dependent of some subject characteristics. After adjusting for other predictors, the HG program induced a higher ΔBMD on lumbar spine of postmenopausal women while femoral neck ΔBMD was not impacted by either program. Supported by the Portuguese Foundation for Science (Sapiens 358007/99)

Reproducibility of volume-adjusted bone mineral density of spine and hip from dual X-ray absorptiometry.

Skeletal size has a confounding effect on areal bone mineral density (aBMD) related to differences in skeletal volume. Several methods have been proposed for calculating volumetric BMD (vBMD), but in vivo precision data are limited for the spine and have not been published for the hip. We prospectively performed duplicate dual X-ray absorptiometry measurements of the anteroposterior spine and hip (n = 121) in a diverse female population referred for initial clinical BMD testing. Each scan pair was performed and analyzed by two different technologists (mean interval of 4 d) to obtain standard aBMD. Scan data were reprocessed at a later date to calculate vBMD for the lumbar spine (L2-L4), femoral neck, and total hip in the 87 spines and 82 hips for which we had complete analyzable scan data. We found much worse precision in femoral neck volume (5.2% coefficient of variation [CV]) than in spine volume (2.6% CV; p < 0.003). This contributed to greater error in femoral neck vBMD (3.9% CV) than aBMD (2.3= CV; p < 10(-6)). Total hip aBMD had better precision than vBMD (1.0 and 1.3-2.5% CV; p < 10(-5)). The reverse pattern was seen in the spine with slightly better precision for vBMD than aBMD (1.1 and 1.5% CV; p < 0.002). Volumetric measures of lumbar spine density can be obtained with high precision. Because of poor reproducibility in the femoral neck, the total hip region may be preferable for measuring volumetric bone density in the proximal femur.

BONE MINERAL DENSITY (BMD) OVER TIME IN PEDIATRIC RENAL TRANSPLANT (TX) PATIENTS.

900 BMD of the spine and total body in pediatric renal TX patients decreases with age and years post-TX. To evaluate BMD over time in pediatric renal TX patients, we studied 21 pediatric renal TX patients with BMD of spine and total body by dual energy x-ray absorption at entry to the study and at follow-up (FU) 1.4±0.4 (X±SD) years later. Age, weight, total prednisone dose since transplant, serum calcium, phosphorus, and creatinine were recorded at initial exam and at FU. Age was 15±4 years at FU. Time post-TX at initial evaluation was 2.2±2.0 years and at FU was 3.6±1.9 years. Serum calcium, phosphorus, and creatinine were within the normal range at both initial exam and FU in all patients. Maintenance immunosuppression consisted of prednisone, cyclosporine, and azathioprine in all patients. Total body BMD Z score at FU inversely correlated with time on dialysis+time post-TX+FU time (r=−0.50,p=0.022). At initial exam spine BMD Z score correlated with total body BMD Z score (r=0.91, p<0.001); at FU spine BMD Z score also correlated with total body BMD (r=0.75,p<0.001). During FU, spine BMD Z score decreased 0.48±1.06 (paired t=2.09,p=0.049) and total body BMD Z score decreased 0.31±0.66 (paired t=2.18, p=0.042). The change in spine BMD Z score from initial to FU exam correlated with age (r=0.49,p=0.023), cumulative prednisone dose from initial to FU exam (r=0.60, p=0.004), and cumulative prednisone dose from initial to FU exam per body weight (r=0.70, P<0.001). The change in total body BMD Z score correlated with cumulative prednisone dose from initial to FU exam per body weight (r=0.54, p=0.012). BMD of the spine and total body in pediatric renal TX patients continues to decrease with increasing time post-TX and increasing cumulative corticosteroid dose. Strategies to improve BMD, both initially post-TX and later post-TX, need to be developed for these pediatric renal TX patients.

A concomitant decrease in cortical and trabecular bone mass in isolated hypogonadotropic hypogonadism and gonadal dysgenesis.

To assess the impact of hypogonadism on bone mineral density, we performed a cross-sectional study of 70 amenorrheic women, comprising 22 cases of gonadal dysgenesis and 48 cases of isolated hypogonadotropic hypogonadism (IHH). Bone mineral density was measured by DEXA at four sites: the femur neck, Ward's triangle, trochanter, and lumbar spine (L2-4). The results were compared to those of a control group consisting of 60 age-matched, normal-cycling women. Bone mineral densities around age 20 were already significantly lower at all four sites in patients with IHH and gonadal dysgenesis when compared with controls, suggesting that these patients failed to achieve peak bone mass during pubertal development. In patients with IHH, the initial BMD around age 18-20 were significantly lower at all four sites and the decrease in bone density continued rapidly during the early twenties up to age 25, and then it slowed markedly thereafter. Bone biochemical marker, ICTP and osteocalcin were significantly negatively correlated with age and remained increased until age 40, which was reminiscent of menopausal bone loss pattern such as high bone turn-over in the early twenties, followed by slow bone loss in the late twenties. In patients with gonadal dysgenesis, bone biochemical marker, ICTP and osteocalcin were also significantly negative correlated with age and remained increased until age 40, but no significant changes in BMD were noted as a function of age, which may be attributed to the small sample size and slow bone loss. These findings suggest that the initiation of prompt and timely therapeutic intervention as early as possible in the menarchal period and throughout the remainder of life, particularly during the period associated with rapid bone loss.

Dairy Supplementation Prevents Seasonal None Loss in Elderly Women

Seasonal decrements in femoral and lumbar bone mass among postmenopausal women have recently been reported by several groups. However, previous studies have been relatively short-term or observational. We now report interim one year results from a two year randomized double blinded(single blinded for dietary), placebo controlled calcium intervention study in elderly women. Sixty active but older postmenopausal women (mean age 72 years: range 61-88 years) with mean daily calcium intake of 571± 50mg/day were randomized to one of three intervention arms: 1) Placebo-Calcium (PC) twice daily (n=20); 2) CaC03 (CC) n=21: two 500mg tablets with meals; 3) Dietary Calcium (DC) milk, 3–3.5 glasses/day to a total .daily intake of 1200mg/day; (n=19). Bone mineral density of the spine (L2-L4) and greater trochanter of the hip (GT) were measured by DXA at six month intervals (longitudinal c.v. = 1.0% spine, 2.0%-GT). The six month intervals were October-March (winter,), April-September (summer,). DC women were telephoned frequently while all women were seen for non-calcium dietary discussions at three and nine months. Grocery slips were monitored for the DC group and compliance was assessed by urinary calcium clearance, dietary records (4 day food records) and food frequency questionnaire. Vitamin D content of the milk was also measured. Sixty women began the study and 53 women completed 12 months. Only one subject dropped out in the DC group. Initial BMD (L2–L4 and GT) did not differ among groups, nor did age, height, weight or initial Ca intake. Among DC women, no significant change in weight was noted. Calcium intake and % change in BMD(± SEM) are noted below:In conclusion: 1) Among elderly women in northern New England who consume low calcium diets, seasonal bone loss from both cortical and trabecular sites is significant; 2) annual declines in BMD within this cohort occur only during late fall and winter; 3) DC or CC are equally effective in preventing winter time bone loss from the L-spine, but only DC prevented bone loss from occurring in the GT, 4) consumption of milk products (to 1200mg/day) was well tolerated and resulted no significant weight change, 5) there are differential effects on conical bone mass between CC and DC which may reflect differences in calcium bioavailability or mechanisms of action distinct from calcium alone Funded by the National Dairy Promotion and Research Board and administered in cooperation with the National Dairy Council.