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Biomedical subjects

P R Ebeling

Publications and source records attributed to P R Ebeling.

At least 19 recordsLinked to original sources
PubMed1999

Mechanisms of bone loss following allogeneic and autologous hemopoietic stem cell transplantation.

A significant proportion of patients will be long-term survivors of bone marrow transplantation (BMT) and little is known about their risk of late bony complications. We therefore evaluated bone mineral density (BMD) prior to BMT, post-transplantation changes in BMD, and mechanisms of bone loss in long-term survivors. We performed two analyses. The first was a cross-sectional study of 83 consecutive BMT patients (38 F, 45 M), examining the relationship between BMD and bone turnover, measured immediately prior to transplantation, and a number of disease and patient variables. The second was a prospective study of 39 patients (19F, 20 M) followed for a median of 30 months (range 5-64 months) following either allogeneic (allo, n = 29) or autologous (auto, n = 10) BMT to determine if bone loss was related to treatment of graft versus host disease (GVHD) with glucocorticoids and cyclosporine A, high bone turnover rates, or hypogonadism. Auto BMT recipients acted as a control group for effects of GVHD therapy on BMD. Prior to BMT, spinal and femoral neck (FN) BMDs were 8.6% and 14% lower in female auto BMT recipients than in female allo BMT recipients, respectively (p = 0.12 and p = 0. 003). Urinary bone resorption markers were higher than in normal gender- and age-matched control subjects. Patients treated previously with glucocorticoids also had 8% lower FN BMD. Glucocorticoid-pretreated women with amenorrhoea had lower lumbar spine (LS) and FN BMDs than eumenorrheic women and women receiving HRT. Post-allo BMT, patients lost 11.7% of FN BMD compared with a nonsignificant decrease of 1.1% post-auto BMT (p < 0.001). Spinal BMD and total body bone mineral content (TBBMC) decreased by 3.9% and 3.5%, respectively, post-allo, compared with an increase (1.5%, p = 0.03) or nonsignificant decrease (-3.7%, p = NS), respectively, post-auto BMT. Post-allo BMT bone loss correlated best with the cumulative prednisolone dose at the LS and FN, and with average daily prednisolone dose for TBBMC. At the spine, the rate of bone loss was 4%/10 g of prednisolone, while the rate of bone loss at the FN was greater (9%/10 g of prednisolone). Bone loss was also negatively related to the duration of cyclosporine therapy for GVHD and baseline deoxypyridinoline concentrations. Avascular necrosis of the femoral head occurred in four, and vertebral and rib fractures occurred in one of the allo BMT patients, but in no auto BMT patients. In conclusion, BMT recipients are at risk of osteoporosis secondary to bone loss associated with their underlying illness and/or chemotherapy, particularly in female autograft recipients, and in allograft recipients secondary to GVHD and its treatment.

Adult↗
PubMed1998

A prospective study of bone loss in menopausal Australian-born women.

Two hundred and twenty-four women (74 pre-, 90 peri-, 60 post-menopausal), aged 46-59 years, from a population-based cohort participated in a longitudinal study of bone mineral density (BMD). BMD was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and femoral neck and the time between bone scans was on average 25 (range 14-41) months. The aim of the study was to assess changes in BMD in relation to changes in normal menopausal status. During the study period women who were between 3 and 12 months past their last menstrual period (n = 22, late perimenopausal) at the time of the second bone scan had a mean (SE) annual change in BMD of -0.9% (0.4%) at the lumbar spine and -0.7% (0.6%) at the femoral neck (both p < 0.05 compared with women who remained premenopausal). In the women who became postmenopausal (n = 42) the mean annual changes in BMD were -2.5% (0.2%) at the lumbar spine and -1.7% (0.2%) at the femoral neck (both p < 0.0005), and in the women who remained post-menopausal (n = 60) they were -0.7% (0.2%) per year and -0.5% (0.3%) per year respectively (both p < 0.05), compared with women who remained premenopausal. In the 1-3 years after the final menstrual period (FMP) there was greater bone loss from the lumbar spine than the femoral neck (p < 0.05). In women who were menstruating at the time of the second bone scan and whose FMP could be dated prospectively (n = 35), higher baseline oestradiol levels were associated with less lumbar spine bone loss (p < 0.005). In the women who remained postmenopausal there was an association between baseline body mass index (BMI) and percentage change per year in femoral neck BMD (p < 0.05), such that women with higher BMI had less bone loss. In conclusion, during the time of transition from peri- to post-menopause, women had accelerated BMD loss at both the hip and spine.

Absorptiometry, Photon↗
PubMed1998

A 12-month prospective study of the relationship between stress fractures and bone turnover in athletes.

Bone remodeling may be involved in the pathogenesis of stress fractures in athletes. We conducted a 12-month prospective study to evaluate bone turnover in 46 female and 49 male track and field athletes aged 17-26 years (mean age 20.3; SD 2.0) 20 of whom developed a stress fracture. Baseline levels of bone turnover were evaluated in all athletes and monthly bone turnover levels were evaluated in a subset consisting of the 20 athletes who sustained a stress fracture and a matched comparison group who did not sustain a stress fracture. Bone formation was assessed using serum osteocalcin (OC) measured by human immunoradiometric assay and bone resorption by urinary excretion of pyridinium cross-links (Pyr and D-Pyr); high performance liquid chromatography and N-telopeptides of type 1 collagen (NTx) using ELISA assay. Athletes who developed stress fractures had similar baseline levels of bone turnover compared with their nonstress fracture counterparts (P > 0.10). Results of serial measurements showed no differences in average levels of Pyr, D-Pyr, or OC in those who developed stress fractures (P = 0.10) compared with the control group. In the athletes with stress fractures, there was also no difference in bone turnover levels prior to or following the onset of bony pain. Our results show that single and multiple measurements of bone turnover are not clinically useful in predicting the likelihood of stress fractures in athletes. Furthermore, there were no consistent temporal changes in bone turnover associated with stress fracture development. However, our results do not negate the possible pathogenetic role of local changes in bone remodeling at stress fracture sites, given the high biological variability of bone turnover markers and the fact that levels of bone turnover reflect the integration of all bone remodeling throughout the skeleton.

Adolescent↗
PubMed1998

Lambda light chain induced nephropathy: a rare cause of the Fanconi syndrome and severe osteomalacia.

The Fanconi syndrome is a generalized disorder of proximal renal tubular transport characterized by wasting of phosphate, amino acids, glucose, bicarbonate, and uric acid. The association of the acquired Fanconi syndrome with lambda light-chain proteinuria is rare. We report the third case in the English language literature. A 65-year-old man presented with severe pelvic pain. Investigations showed an elevated serum creatinine level, and a 24-hour urine collection contained 2.56 g protein. The Fanconi syndrome was diagnosed, with findings of phosphaturia, glycosuria, and aminoaciduria. Bence Jones protein (lambda sub-type) was present in the urine at a concentration of 0.58 g/L. Monocytic cells in the bone marrow and proximal tubular cells in the kidney contained cytoplasmic crystalline inclusions. Undecalcified bone sections confirmed the clinical diagnosis of osteomalacia. The patient was treated with phosphate, calcium, and ergocalciferol and experienced significant symptomatic improvement. The Fanconi syndrome caused by light-chain deposition in proximal tubular cells is well described in the literature. However, it is rare for the light chains to be of the lambda subtype. This may reflect differences in the physicochemical properties of kappa and lambda light chains.

Aged↗
PubMed1998

Bone mineral density and bone turnover in asthmatics treated with long-term inhaled or oral glucocorticoids.

Inhaled glucocorticoids are pivotal in maintenance therapy of chronic bronchial asthma; however, conflict exists over their effects on bone and mineral metabolism. We measured bone mineral density (BMD), bone turnover markers, and adrenal steroid hormones in 53 patients (34 female, 19 male) with chronic bronchial asthma who had taken either inhaled beclomethasone or budesonide in doses of > or = 1500 microg/day for at least 12 months to determine pathogenetic mechanisms of bone loss. To account for the effect of prior oral glucocorticoid exposure we divided patients into two groups: one with (OG) and the other without (IG) a past history of maintenance (> 1 month) oral glucocorticoid therapy. Lumbar spine (LS) and proximal femur BMDs were approximately 1 SD lower in men and women taking OG or high-dose IG for chronic bronchial asthma, potentially equivalent to a doubling of the risk of fracture at these sites. Prior exposure to OG in women was also associated with lower LS and proximal femur BMDs, while men were more sensitive to the adverse effects of IG on LS and Ward's triangle BMDs. Bone formation markers were decreased; however, bone resorption marker concentrations were normal. All patients had evidence of suppression of both endogenous glucocorticoid and adrenal androgen production. Both total duration of OG and biochemical bone turnover marker concentrations were negatively related to proximal femur and rib BMDs and total body bone mineral content, but not to LS BMD. These were stronger for bone resorption markers. Uncoupling of ongoing normal bone resorption from suppressed bone formation may therefore contribute to glucocorticoid-associated bone loss in asthma. Adrenal androgen suppression may also increase the susceptibility of postmenopausal women in particular to bone loss with OG. Although the effects of high-dose IG on BMD are associated with lower LS BMD in men, this observation should now be investigated further in prospective studies.

Absorptiometry, Photon↗
PubMed1998

Osteoporosis in men. New insights into aetiology, pathogenesis, prevention and management.

Osteoporosis is increasingly recognised in men. Low bone mass, risk factors for falling and factors causing fractures in women are likely to cause fractures in men. Bone mass is largely genetically determined, but environmental factors also contribute. Greater muscle strength and physical activity are associated with higher bone mass, while radial bone loss is greater in cigarette smokers or those with a moderate alcohol intake. Sex hormones have important effects on bone physiology. In men, there is no abrupt cessation of testicular function or 'andropause' comparable with the menopause in women; however, both total and free testosterone levels decline with age. A common secondary cause of osteoporosis in men is hypogonadism. There is increasing evidence that estrogens are important in skeletal maintenance in men as well as women. Peripheral aromatisation of androgens to estrogens occurs and osteoblast-like cells can aromatise androgens into estrogens. Human models exist for the effects of estrogens on the male skeleton. In men aged > 65 years, there is a positive association between bone mineral density (BMD) and greater serum estradiol levels at all skeletal sites and a negative association between BMD and testosterone at some sites. It is crucial to exclude pathological causes of osteoporosis, because 30 to 60% of men with vertebral fractures have another illness contributing to bone disease. Glucocorticoid excess (predominantly exogenous) is common. Gastrointestinal disease predisposes patients to bone disease as a result of intestinal malabsorption of calcium and colecalciferol (vitamin D). Hypercalciuria and nephrolithiasis, anticonvulsant drug use, thyrotoxicosis, immobilisation, liver and renal disease, multiple myeloma and systemic mastocytosis have all been associated with osteoporosis in men. It is possible that low-dose estrogen therapy or specific estrogen receptor-modulating drugs might increase BMD in men as well as in women. In the future, parathyroid hormone peptides may be an effective treatment for osteoporosis, particularly in patients in whom other treatments, such as bisphosphonates, have failed. Men with idiopathic osteoporosis have low circulating insulin-like growth factor-1 (IGF-1; somatomedin-1) concentrations, and IGF-1 administration to these men increases bone formation markers more than resorption markers. Studies of changes in BMD with IGF-1 treatment in osteoporotic men and women are underway. Osteoporosis in men will become an increasing worldwide public health problem over the next 20 years, so it is vital that safe and effective therapies for this disabling condition become available. Effective public health measures also need to be established and targeted to men at risk of developing the disease.

Adult↗
PubMed1997

Bone mass and bone turnover in power athletes, endurance athletes, and controls: a 12-month longitudinal study.

Strain magnitude may be more important than the number of loading cycles in controlling bone adaptation to loading. To test this hypothesis, we performed a 12 month longitudinal cohort study comparing bone mass and bone turnover in elite and subelite track and field athletes and less active controls. The cohort comprised 50 power athletes (sprinters, jumpers, hurdlers, multievent athletes; 23 women, 27 men), 61 endurance athletes (middle-distance runners, distance runners; 30 women, 31 men), and 55 nonathlete controls (28 women, 27 men) aged 17-26 years. Total bone mineral content (BMC), regional bone mineral density (BMD), and soft tissue composition were measured by dual-energy X-ray absorptiometry. Bone turnover was assessed by serum osteocalcin (human immunoradiometric assay) indicative of bone formation, and urinary pyridinium crosslinks (high-performance liquid chromatography) indicative of bone resorption. Questionnaires quantified menstrual, dietary and physical activity characteristics. Baseline results showed that power athletes had higher regional BMD at lower limb, lumbar spine, and upper limb sites compared with controls (p < 0.05). Endurance athletes had higher BMD than controls in lower limb sites only (p < 0.05). Maximal differences in BMD between athletes and controls were noted at sites loaded by exercise. Male and female power athletes had greater bone density at the lumbar spine than endurance athletes. Over the 12 months, both athletes and controls showed modest but significant increases in total body BMC and femur BMD (p < 0.001). Changes in bone density were independent of exercise status except at the lumbar spine. At this site, power athletes gained significantly more bone density than the other groups. Levels of bone formation were not elevated in athletes and levels of bone turnover were not predictive of subsequent changes in bone mass. Our results provide further support for the concept that bone response to mechanical loading depends upon the bone site and the mode of exercise.

Adolescent↗
PubMed1997

Evaluation of a new, rapid and automated immunochemiluminometric assay for the measurement of serum intact parathyroid hormone.

The Immulite parathyroid hormone (PTH) immunochemiluminometric assay (ICMA) was evaluated by measuring serum PTH concentrations in 134 volunteers and 25 patients with various diseases affecting bone and mineral metabolism and comparing with those measured by the Nichols Allegro immunoradiometric (IRMA) assay. Although the assays were highly correlated (r = 0.99. P < 0.0001), there were discrepancies at lower PTH concentrations which may be explained by the lower limit of detection of the ICMA assay. The anti-coagulants EDTA and heparin appeared to have significant effects on PTH measurement particularly at lower concentrations. Sera assayed by ICMA diluted out more uniformly than in the IRMA and there was no cross reactivity with parathyroid hormone-related peptide in either the IRMA or ICMA. Delays of up to 8 h in specimen handling did not appear to affect PTH measurements. The enhanced sensitivity of the Immulite ICMA intact PTH assay confers an advantage in the diagnosis of both hyper- and hypocalcaemia, while the shorter incubation times, automation and lack of radioactivity are important practical advantages.

Adolescent↗
PubMed1997

Premenopausal ovariectomy-related bone loss: a randomized, double-blind, one-year trial of conjugated estrogen or medroxyprogesterone acetate.

The purpose of this study was to contrast the effects of conventional estrogen treatment with medroxyprogesterone on cancellous and cortical bone change in the first year following premenopausal ovariectomy. This 1-year double-blind randomized therapy trial was stratified by osteoporosis family history and performed in an academic medical center and community hospitals. Premenopausal women 45 +/- 5 years old, postovariectomy for benign diseases were provided 600 mg/day of calcium and randomized to daily therapy with conjugated equine estrogen (CEE, 0.6 mg) or medroxyprogesterone (MPA, 10 mg). The primary outcome variable was spinal quantitative computed tomography (QCT) bone density change over 1 year with additional outcomes of dual-energy X-ray absorptiometry (DXA) of proximal femur (FN), whole body (WB), and spine segment (WBS) and N-telopeptide, bone-specific alkaline phosphatase, and other bone marker, hormonal, and weight changes. Results in the 33 women completing the study, whose initial bone densities were normal (QCT 133 mg/cm3, femoral neck 0.94 g/cm2, whole body DXA 1.13 g/cm2), showed annual QCT loss during CEE therapy of -11.5 mg/cm3 (p < 0.0007) and MPA bone loss of -19.7 mg/cm3 (p < 0.0001). Losses were marginally greater on MPA than CEE (p = 0.04). Extremely high postovariectomy (5 days) and pretreatment resorption markers (> 3 SD above premenopausal normal levels) were significantly related to bone loss. Across the year, resorption decreased during CEE but increased on MPA treatment. Significant DXA bone losses were prevented by CEE treatment (-1.4% FN, -.4% WB, and -1.5% WBS, all NS). However, DXA bone loss was not prevented by MPA treatment (-5% FN, -2.8% WB, and -6.1% WBS, all p < 0.03). Average weight gain was significant (+ 3.2 +/- 4.0 kg) and greater on CEE than MPA (+ 4.7 vs. + 2.0 kg, p = 0.049). In conclusion, CEE therapy did not prevent significant 8% cancellous spinal bone loss in the first year following premenopausal ovariectomy, despite supplementation with 600 mg/day of calcium, good control of vasomotor symptoms, and nearly 5 kg of gain in weight. Significant DXA bone loss, however, was prevented by CEE, but not by MPA therapy. These unexpected results were statistically related to high bone resorption following ovariectomy, which CEE suppressed but MPA did not. Bone formation markers increased during MPA therapy but were unchanged during CEE therapy.

Absorptiometry, Photon↗
PubMed1997

Large, rapid skeletal changes after parathyroidectomy.

We report dramatic increases in spine and hip bone mineral density six weeks following parathyroidectomy in renal patients. We have previously reported a cross-sectional association between parathyroidectomy and higher axial bone mineral density in dialysis patients. Large axial increases in bone mineral density after surgery for primary hyperparathyroidism have been recorded by others at one year postoperatively. Bone mineral density was recorded before and six weeks after parathyroidectomy. Scans were performed at the lumbar spine, hip and non-dominant radius. Values were expressed as Z-scores (standard deviations from the mean of an age- and gender-matched reference population). Large increases in lumbar were spine and femoral neck bone mineral density seen at six weeks post parathyroidectomy. Median increases were 0.57 (p = 0.006) and 0.26 (p = 0.039) Z-score units for these sites, respectively. Individual six-week increases were as large as 1.3 Z-score units at the spine and 1.0 Z-score units at the femoral neck. No significant cohort change was detected at the forearm but individual forearm changes were highly variable. Several mechanisms to explain these large rapid increases can be postulated. These include: mineralization of osteoid and/or contraction of the remodeling space. The changes illustrate the extent to which the skeleton is capable of rapid and profound change in mineral content. Our findings emphasize that the skeleton is a heterogeneous organ and that bone density should be measured at multiple skeletal sites.

Absorptiometry, Photon↗
PubMed1996

Prevalence and risk factors for osteopenia in dialysis patients.

Dialysis patients are at risk for low bone mineral density (BMD) consequent of hyperparathyroidism, 1,25-dihydroxyvitamin D deficiency, previous immunosuppression, chronic acidosis, secondary amenorrhea, and chronic heparin and aluminum exposure. We wanted to determine the prevalence and distribution of osteopenia and the influence of risk factors for osteopenia in dialysis patients. Dual energy x-ray absorptiometry was used to record BMD at the lumbar spine (LS), hip, and nondominant forearm. Results were expressed as Z-scores (standard deviations from the mean of a healthy age- and gender-matched reference population). Osteopenia was defined as a Z-score worse than -2. In the 250 dialysis patients studied, the prevalence of osteopenia at the LS, femoral neck (FN) and ultradistal radius (UD) was 8%, 13% and 20%, respectively. The median Z-scores at these sites were all significantly different from the healthy reference population median of 0 and were 0.29 (P = 0.008), -0.67 (P < 0.001), and -1.01 (P < 0.001), respectively. Previous transplantation was associated with as much as a one Z-score lower BMD at the FN (P = 0.0069) and UD (P = 0.0011) and a marginally significant reduction at the LS (P = 0.0777). Previous parathyroidectomy was associated with a markedly higher LS BMD (P = 0.0001) and a higher BMD at the FN (P = 0.0017) but not the UD (P = 0.3691). A history of secondary amenorrhea was associated with a lower FN BMD (P = 0.0047) but not a significantly lower BMD at the LS (P = 0.0978) or UD (P = 0.2327). In hemodialysis patients without a history of transplantation, parathyroidectomy, or secondary amenorrhea, there was no correlation between Z-score at any site and duration of dialysis. Thus, osteopenia in dialysis patients occurs in both axial and appendicular sites and sites of compact and cancellous bone. It is more common with previous transplantation and secondary amenorrhea, whereas a history of parathyroidectomy is associated with increased BMD. No relationship was found between BMD and duration of hemodialysis, which suggests that important changes in BMD occur during the predialysis stage of chronic renal failure.

Absorptiometry, Photon↗
PubMed1996

Risk factors for secondary hyperparathyroidism in a nursing home population.

OBJECTIVE: Secondary hyperparathyroidism may cause bone loss and structural deterioration of bone and may thus be a cause of fracture in the elderly. Vitamin D deficiency, renal impairment and medications are potential causes of hyperparathyroidism and may also directly predispose to fracture. We present the first findings of an ongoing study of hip fracture, vitamin D deficiency and hyperparathyroidism in a large Australian nursing home. DESIGN: Descriptive prevalence study. PATIENTS: Two hundred and fifty-one nursing home residents were eligible for inclusion. Informed consent and successful venepuncture were obtained for 99. Residents were of median age 83 years with interquartile range (IR) 77-89 years. MEASUREMENTS: 25-Hydroxyvitamin D (25OHD), intact parathyroid hormone (PTH), creatinine and biochemistry, demographic data and current medications. RESULTS: Fifty-two per cent of 99 subjects had 25OHD below the reference range of 28-165 nmol/l and 96.5% were below the reference range mean. Those with low 25OHD had lower plasma calcium corrected for albumin than those with normal 25OHD (medians 2.34 vs 2.41 mmol/l, 95% confidence interval for the difference between medians (CI) -0.10 to -0.04 mmol/l, P = 0.0001) and higher PTH (medians 5.8 vs 3.9 pmol/l, CI 0.10-2.6 pmol/l, P = 0.0360). Twenty-eight per cent of 97 residents had PTH above the upper reference range limit of 6.5 pmol/l. Residents receiving frusemide had higher PTH than other residents (medians 6.95 vs 3.45 pmol/l, CI 1.9-4.2 pmol/l, P < 0.0001). In linear modelling, the most important predictor of the natural logarithm of PTH was daily frusemide dose, adjusted R2 (Ra2) = 31.8%, F = 39.3, P < 0.001. Creatinine and the reciprocal of 25OHD were other significant predictors with the final Ra2 = 39.4%, F = 17.7, P < 0.001. CONCLUSIONS: Vitamin D deficiency is a common risk factor for secondary hyperparathyroidism in nursing home residents despite a climate in which vitamin D nutrition is thought to be ample. However, the daily frusemide dose is a more important predictor of PTH in this population.

25-Hydroxyvitamin D 2↗
PubMed1996

Changes in quantitative bone histomorphometry in aging healthy men.

Changes in bone mineral metabolism with aging in healthy men and the roles of various factors in the pathogenesis of age-related changes in quantitative bone histomorphometry in men are poorly defined. To clarify these changes and factors, serum and urinary biochemical parameters and iliac crest bone biopsies were evaluated in 43 healthy men, aged 20-80 yr. The static histomorphometric parameters, cancellous bone volume and osteoblast-osteoid interface, decreased by 40.0% and 19.2%, respectively, between 20-80 yr of age. The dynamic histomorphometric parameters, double and single labeled osteoid, also decreased by 18.6% and 18.0%, respectively, over this period. None of the other static or dynamic histomorphometric parameters changed with age in this population sample of healthy men. Univariate analysis of static bone histomorphometric parameters and biochemical parameters revealed significant correlations between osteoid surface and intact PTH (r = 0.37; P = 0.015); osteoclast surface and serum total testosterone (r = 0.36; P = 0.016), estradiol (r = 0.40; P = 0.009), and FSH (r = 0.49; P = 0.001); osteoblast-osteoid interface and serum phosphate (r = 0.31; P = 0.046); and cortical thickness and serum total calcium (r = 0.38; P = 0.013). Univariate analysis of dynamic bone histomorphometric parameters and biochemical parameters revealed correlations between mineral apposition rate and serum total testosterone (r = 0.32; P = 0.037); total volume-referent bone formation rate and serum osteocalcin (r = 0.43; P = 0.004), total testosterone (r = 0.47; P = 0.001), estradiol (r = 0.35; P = 0.023), and dehydroepinadrosterone sulfate (r = 0.31; P = 0.045); and mean wall thickness and serum total calcium (r = 0.36; P = 0.019) and creatinine clearance (r = 0.42; P = 010). Mineralization lag time and serum phosphate (r = -0.39; P = 0.012) and urinary total pyridinoline (r = 0.36; P = 0.023), and mean wall thickness and urinary total pyridinoline (r = -0.38; P = 0.013), were inversely correlated. Multiple regression analysis using all-subset analysis comparing cancellous bone volume to serum and urinary biochemical parameters in these men indicated that the log free androgen index and body weight best predicted the age-related decline in iliac crest cancellous bone volume (r2 = 0.19; P = 0.015). Multiple regression analysis by the same method, comparing bone density at different skeletal sites to bone histomorphometric parameters, indicated that lumbar spine bone mineral density (BMD) was best predicted by cancellous bone volume and mineral apposition rate (r2 = 0.31; P = 0.001), femoral neck BMD by cancellous bone volume and osteoid surface (r2 = 0.19; P = 0.020), femoral greater trochanter BMD by cortical thickness and single labeled osteoid surface (r2 = 0.13; P = 0.060), and total body BMD by cancellous bone volume and surface-based bone formation rate (r2 = 0.31; P = 0.001). In summary, cancellous bone volume, osteoblast-osteoid interface, and double and single labeled osteoid decreased with age in this sample of healthy men. The lack of detectable change in bone density at some skeletal sites in these men may be due to the small sample size or other confounding factors. Multivariate analysis suggests that different combinations of histomorphometric parameters predict bone density at different skeletal sites, and that cancellous bone volume predicts bone density at the lumbar spine, femoral neck, and total body, but not at the femoral greater trochanter. We conclude that alterations in several biochemical parameters are important in the pathogenesis of age-related bone loss in healthy men.

Adult↗
PubMed1996

Bone turnover markers and bone density across the menopausal transition.

We measured lunbar spine and femoral neck bone mineral density (BMD); urine markers of bone resorption; serum markers of bone formation; and serum gonadotrophin, estradiol and inhibin concentrations in a population-based cohort of 281 women aged 45-57 yr. Women were classified into pre-, peri-, and postmenopausal groups, depending on menstrual bleeding patterns. Compared with premenopausal women, BMD was lower only in postmenopausal women but not in women currently using hormone replacement therapy (HRT). BMD decreased with age in the perimenopausal group. Compared with premenopausal women, perimenopausal women had 20% greater urine N-telopeptide excretion (P < 0.05) and a doubling of gonadotrophin levels (P < 0.01), whereas serum estradiol and bone formation marker concentrations were no different. Postmenopausal Women had greater levels of bone turnover markers (P < 0.0001), except free deoxypyridinoline and type I procollagen propeptide. Among postmenopausal women, bone resorption markers were lower in those using HRT. Levels of nearly all bone turnover markers were positively related to serum FSH concentrations (P < 0.0001). Overall, the major independent predictors of BMD were age, urine N-telopeptide, serum bone alkaline phosphatase, and serum, FSH, whereas urine free deoxypyridinoline was positively related to BMD in pre- and perimenopausal women. In conclusion, the perimenopause is associated with elevated bone resorption rates and declining BMD, and factors in addition to estrogen deficiency may also contribute to the pathogenesis of postmenopausal osteoporosis.

Aging↗
PubMed1996

Bone mineral density and hormone levels in menopausal Australian women.

To assess the relationships between bone mineral density (BMD) at the lumbar spine and femoral neck and menopausal status, age, physical variables, and lifestyle and gynecological factors. BMD and follicle-stimulating hormone (FSH), estradiol and inhibin levels were measured in 167 women born in Australia, aged 46-57 years, who had no record of receiving hormone replacement therapy. Using the premenopausal group as a baseline, the FSH level was higher in peri- and postmenopausal subjects (p < 0.0005), and estradiol and inhibin levels in the postmenopausal women were lower (p < 0.0005). Mean (+/- SE) lumbar spine and femoral neck BMD were 15 +/- 3% and 10 +/- 3% lower, respectively, in postmenopausal than in premenopausal women. Lumbar spine BMD decreased with increasing age in perimenopausal women only (p < 0.005), and femoral neck BMD decreased with increasing age in the pre-, peri-(p < 0.05) and postmenopausal women. The difference between femoral neck BMD in the pre- and postmenopausal women was explained by the difference in age between these groups, whereas for lumbar spine BMD the menopausal status was an additional determining factor. There was a negative effect of smoking on femoral neck BMD (p < 0.05) in postmenopausal women. In the perimenopausal decade the femoral neck BMD is primarily dependent on age, whereas lumbar spine BMD is dependent on both age and menopausal status.

Aging↗
PubMed1995

Risk factors for stress fractures in female track-and-field athletes: a retrospective analysis.

The incidence and nature of stress fractures and the relationship of potential risk factors to stress-fracture history were investigated retrospectively in a group of 53 female competitive track-and-field athletes. Forty-five stress fractures, diagnosed by clinical findings and bone scan, radiograph, or CT scan, were reported in 22 women. Tibial fractures were the most common (33%). There was no significant difference in bone mineral density at the lumbar spine and tibia/fibula or in percentage body fat and total lean mass when comparing the groups with and without a stress-fracture history. Athletes with a past stress fracture were significantly older at menarche and were more likely to have experienced a history of menstrual disturbance (p < 0.05). Analysis of dietary behavior found that athletes with stress fractures scored significantly higher on the EAT-40 test and were more likely to engage in restrictive eating patterns and dieting. Multiple logistic regression showed that athletes with a history of oligomenorrhea were six times more likely to have sustained a stress fracture in the past, while those who were careful about their weight were eight times more likely. Prevention and treatment of stress fractures in female athletes should include a thorough assessment of menstrual characteristics and dietary patterns.

Adipose Tissue↗
PubMed1995

Bone mineral density and body composition in congenital adrenal hyperplasia.

The purpose of this study was to assess whether replacement doses of glucocorticoid hormones administered to patients with congenital adrenal hyperplasia (CAH) cause changes in body composition, including either generalized or regional osteoporosis. In 21 patients with 21-hydroxylase deficiency we measured height, body mass index, lean mass, fat mass, and whole body and regional bone mineral density (BMD). We measured the same parameters in 21 age- and sex-matched control patients. The CAH group (aged 8-32 yr) showed significantly reduced mean height compared with both standard data (P = 0.0015) and the control group (P = 0.009). There were no significant differences in mean body mass index between the CAH group and the standard data (P = 0.13) or the control group (P = 0.87). CAH males had significantly higher fat/lean mass ratios than control males (P = 0.005). There were no significant differences in whole body mean bone mineral apparent density values between the CAH and control groups (P = 0.39). There were, however, significant differences in whole body BMD z scores between the CAH and control groups and the reference data (P = 0.027 and P = 0.004, respectively). No significant differences were observed between the total CAH and control groups with respect to spinal bone mineral apparent density; however CAH males had significantly lower mean adjusted spinal BMD than the male controls (P = 0.02). We conclude that although replacement therapy with glucocorticoid and mineralocorticoid hormones in our group of CAH patients may not be optimal with regard to longitudinal growth, it is not deleterious in terms of general bone mineralization. It may decrease spinal BMD in CAH males. We also conclude that the relevance of Hologic reference data for BMD to an Australian population is uncertain, and there is a need for Australian standard data.

Absorptiometry, Photon↗