Cancellous Bone of the Spine is Greater in Black Women

The bone mineral density (BMD) of the spine was measured in the posteroanterior (PA) and lateral projections as well as the total body BMD in 447 black and white women. The lateral projection is comprised predominantly of cancellous bone whereas the total body BMD is predominantly cortical bone, and the PA spine is intermediate in composition. Black women had a higher BMD than white women for each measurement, but the difference was greatest in the lateral spine. Similarly, black women showed less decline in cancellous bone density with aging. The development of a high peak cancellous bone mass with reduced involutional loss may provide a major contribution towards protection against osteoporotic fractures in black women. Metabolic and pharmacologic studies in black and white women should consider the possibility of the influence of a larger cancellous bone mass. Received: 14 November 1997 / Accepted: 11 December 1998     

Calcitonin Provides Complete Protection Against Cancellous Bone Loss in the Femoral Neck of Ovariectomized Rats

Calcitonin (CT) has been found to partially prevent cancellous bone loss in the proximal tibia of ovariectomized (OVX) rats. The current study was designed to determine whether CT has similar bone protective effects in the femoral neck, a skeletal site with a slower rate of bone loss after ovariectomy than the proximal tibia. Female Sprague Dawley rats were sham-operated or ovariectomized at 3 months of age. Groups of OVX rats were injected s.c. with vehicle or CT at a dose of 16 U/kg body weight on alternate days for 30, 60, or 90 days. Sham-operated control rats were treated with vehicle alone on alternate days. The proximal femur from each rat was processed undecalcified for quantitative bone histomorphometry. Cancellous bone volume in the femoral neck of vehicle-treated OVX rats was significantly less than that of vehicle-treated control rats at all time points. This cancellous osteopenia induced by ovariectomy was associated with increased indices of bone turnover such as osteoclast surface, osteoblast surface, and bone formation rate (tissue level, total surface referent). In contrast, cancellous bone volume in the femoral neck of CT-treated OVX rats was nearly identical of that of vehicle-treated control rats throughout the study. In addition, CT treatment of OVX rats decreased all indices of bone turnover to near the level of vehicle-treated control rats. The results indicate that CT treatment depresses bone turnover and provides complete protection against moderate cancellous osteopenia in the femoral neck of OVX rats. Since previous studies have shown that CT only partially protects against more pronounced cancellous bone loss in the proximal tibia of OVX rats, our findings suggest that CT has a greater bone protective effect at a skeletal site with a slower rate of cancellous bone loss (femoral neck) than at a skeletal site with a rapid rate of cancellous bone loss (proximal tibia). Received: 21 August 1996 / Accepted: 10 December 1996     

Prepubertal Oophorectomy Limits the Accumulation of Cancellous Bone in the Femur of Growing Rats with Long-Term Effects on Metaphyseal Bone Architecture

Bone loss after oophorectomy of adult rats is more rapid and complete in the metaphysis than in the epiphysis of the femur, particularly in the proximal region of the metaphysis distant from the growth plate. This study was undertaken to determine the effects of prepubertal oophorectomy on femoral cancellous bone acquisition during growth. Rats were oophorectomized (OVX) or sham operated at 3 weeks of age and killed at intervals up to 78 weeks for scanning electron microscopy and histomorphometry of the distal femur. Differences in cancellous bone architecture between the two groups was evident after 6 weeks of age. Relatively minor differences were found in the part of the metaphysis near the growth plate and in the epiphysis, with less trabeculae in the primary spongiosa and 1 to 2 less trabeculae/mm in the secondary spongiosa. However, as metaphyseal growth proceeded, trabeculae were present for a greater distance up the femoral shaft in controls than in OVX rats, with mean BV/TV in the proximal part of the metaphysis increasing from 1.4% at 6 weeks to 13.4% at 20 weeks in controls, with no increase in the OVX rats. We find that the lack of ovarian hormones increases the rate of destruction of trabeculae near the metaphyseal-diaphyseal junction. Received: 25 February 1997 / Accepted: 17 June 1997     

Estrogen and Cancellous Bone Loss in the Fowl

Female birds model a type of woven bone prior to egg laying which is known as medullary bone. Medullary bone modeling is estrogen dependent and in the female fowl coincides with a decrease in cancellous bone volume. Medullary bone modeling was induced in male laying-strain fowl by the administration of estrogen and prevented in females by the administration of tamoxifen. In estrogen-treated males, medullary bone modeling was accompanied by cancellous bone loss; cancellous bone volume was significantly lower than in control males (P < 0.001). In females, the prevention of medullary bone modeling by tamoxifen treatment resulted in significantly higher cancellous bone volumes than in control females (P < 0.001). Estrogen therefore appears to play a role in cancellous bone loss in the fowl. Received: 29 April 1997 / Accepted: 3 September 1997     

Effects of High-Fat Diet on Mature Bone Mineral Content, Structure, and Mechanical Properties

Diets with a high saturated fat content can produce deleterious effects on the absorption of dietary calcium and consequently an adverse effect on bone mineralization in growing animals. Hence dietary fat may have long-term consequences for skeletal health and skeletal pathologies such as osteoporosis. Whether a diet high in saturated fat has similar negative effects on adult bone, however, remains unresolved. Thus, we investigated effects of a high-fat diet on mature bone structure and mechanics. Adult (40-week-old) roosters were maintained for 20 weeks on either a diet high in saturated fat (HF) or a low-fat (LF) diet. Cortical bone samples (tarsometatarsus) were tested mechanically in three-point bending, and cancellous bone cores from the femoral condyles and tibial plateau (four sites per knee) were tested mechanically in compression. Cortical bone cross-sectional areal data were also compared among the groups, and bone mineral content (BMC) was determined (by ashing) for both cortical bone and cancellous bone samples. There were no significant high-fat diet effects on mature cortical bone mechanical properties, geometric structure, or mineral content. Diet, however, did affect cancellous bone composition. For example, LF cancellous BMC was significantly greater than HF. Mechanical properties of the cancellous bone showed similar trends such that LF cancellous bone strength was consistently greater than HF. The potential for adverse effects of a HF diet on intestinal calcium absorption in the mature animal may be more apparent in cancellous bone, with its faster rate of turnover, than in cortical bone. Changes in cancellous bone structure and mechanical properties, related to dietary saturated fats, may have implications for understanding the role of nutrition in skeletal health and prevention of pathological bone loss (osteoporosis). Received: 27 January 1997 / Accepted: 9 October 1997     

Osteoporosis After Gastrectomy: Bone Mineral Density of Lumbar Spine Assessed by Dual-Energy X-ray Absorptiometry

Although osteoporosis is a common clinical disorder associated with gastric surgery, long-term effects of gastrectomy on bone metabolism are still unclear. The purpose of this study was to clarify the incidence and risk factors of osteoporosis after gastrectomy using univariate and multivariate analyses of quantitative measurements. The study included 59 patients who had undergone gastrectomy more than 5 years before. There were 38 men and 21 women, aged 37–81 years, mean 64 years. Bone mineral density (BMD) of L2–L4 spine was measured using dual-energy X-ray absorptiometry (DXA). Absolute value of BMD (g/cm²) and age- and sex-matched BMD (%) were given. The mean BMD was 0.766 g/cm², and the incidence of osteoporosis (BMD less than 0.70 g/cm²) was 37%: 18% in men and 71% in women. The mean age- and sex-matched BMD was 85.9%: 87.5% in men and 83.1% in women. Univariate and multivariate analyses revealed that BMD was significantly associated with the age and sex of patients, but was not influenced by the type of gastrectomy (partial versus total) and years after operation (<20 versus 20<). Our study clarified the fact that postgastrectomy osteoporosis was frequent in the aged or female patients. BMD should be evaluated after gastrectomy, especially in the aged and in women. Received: 5 January 1998 / Accepted: 13 August 1999     

Biochemical Markers of Bone Turnover and Bone Loss at the Lumbar Spine and Femoral Neck: The Taiji Study

The purpose of this study was to ascertain whether biochemical markers of bone turnover predict bone loss. The survey was carried out in Taiji, Wakayama Prefecture, Japan. From a list of inhabitants aged 40–79 years, 400 participants (50 men and 50 women in each of four age groups) were selected randomly. Bone mineral density (BMD) was measured, and blood and urine samples of all participants were examined to obtain values for eight biochemical markers: alkaline phosphatase (ALP), bone Gla protein (BGP), type I procollagen (carboxyterminal peptide of type I procollagen; PICP), cross-linked carboxyterminal telopeptide region of type I collagen (ICTP), and urinary excretion of calcium (Ca), phosphate (P), pyridinoline (Pyr), and deoxypyridinoline (D-Pyr). Each marker was evaluated as a predictor of the rate of bone change in lumbar spine and femoral neck BMD over a 3-year period. The value of Pyr was significantly related to the change of lumbar spine BMD in men (P= 0.009), and that of BGP was found to be significant in women (P= 0.045). By contrast, none of the bone markers significantly correlated with bone loss at the femoral neck. The coefficient of determination at the lumbar spine was 5% and 7% at the femoral neck only. We conclude that biochemical markers of bone turnover cannot predict bone loss rates in middle-aged or elderly Japanese men and women over a 3-year period with sufficient accuracy for use in clinical decision making. Received: 26 January 1998 / Accepted: 9 July 1998     

Relationship Between Spine Bone Mineral Density and Vertebral Body Heights

The aim of this study was to investigate the correlation between lumbar spine bone mineral density (LS-BMD) and the vertebral body heights with advancing age and years since menopause. One hundred and sixty-three women ages 39–74 years (77 normal premenopausal, ages 39–54, and 86 normal postmenopausal, ages 46–74 years) were studied. LS-BMD was measured by dual energy X-ray absorptiometry. Vertebral heights were evaluated, using morphometry, as the sum of anterior (AHs), middle (MHs), and posterior (PHs) vertebral body heights from T₄ to L₅. The AHs/PHs ratio at the same level was also calculated. AHs, MHs, PHs, and AHs/PHs ratio directly correlated with LS-BMD; the correlations are AHs r = 0.80, P < 0.0001, MHs r = 0.75, P < 0.0001, PHs r = 0.76, P < 0.0001, and AHs/PHs r = 0.66, P < 0.001. Both LS-BMD and AHs are inversely correlated with age, and the regressions fit with both linear and cubic curves. The statistical significance of the correlations persists while maintaining age constant. The linear regression curve of AHs with age indicates that the spine height decrement rate is 2.12 mm/year, corresponding to 7.4 cm in 35 years. AHs decreases immediately after menopause fitting with a cubic curve model, with a decrement rate of about 3 cm in the first 5 years after menopause. We conclude that the measurement of the sum of vertebral body heights could usefully integrate LS-BMD evaluation in the clinical and epidemiological investigation of osteoporosis. Received: 30 May 1997 / Accepted: 14 November 1997     

Age-Related Changes in the Biochemical Properties of Human Cancellous Bone Collagen: Relationship to Bone Strength

The metabolism of bone collagen has received little attention in relation to age-related loss of bone mass and strength. The aim of the present study was to analyze bone collagen content and metabolism in human bone with respect to age. The material consisted of iliac crest bone biopsies from 94 individuals: 46 women (ages 18–96, mean age 60.8 years) and 48 men (ages 23–92, mean age 59.5 years). Excluded from the study were all individuals with known osteoporotic lumbar vertebral fractures and renal, hepatic, or malignant diseases. Prior to collagen analysis the biopsies were scanned in a pQCT scanner for density assessment and then tested biomechanically. The results showed a decline in apparent bone density with age (P < 0.0001), a decline in maximum stress, Young's modulus, and energy absorption with age (P < 0.001). Concomittantly, there was an age-related decline in the intrinsic collagen content with age (P < 0.001). However, there were no biochemical modifications of the bone collagen during aging. There were no significant differences between women and men in the slopes of the regressions-curves. When multiple regression analyses were performed, only apparent bone density came out as a significant contributor in the correlation to biomechanical properties. Nevertheless, the decrease in bone collagen content with age might indicate an increase in the mineralization degree (probably due to decreased bone turnover) and thereby a change in material properties of bone. In conclusion, the present study has shown that loss of bone mass plays the major role in loss of bone strength. However, there is also a change in bone composition during normal aging, leading to a decrease in collagen content and an increase in the degree of mineralization. At this skeletal site, in a normal population there was no change in the biochemical properties of bone collagen. Received: 3 November 1998 / Accepted: 12 March 1999     

Anomalies in the Measurement of Changes in Bone Mineral Density of the Spine by Dual-Energy X-ray Absorptiometry

Dual-energy X-ray absorptiometry (DXA) is frequently used for longitudinal studies of bone mineral status because of the high precision obtained, but evidence is emerging that the accuracy of measurements of changes may be a limitation because of artefacts of the analysis procedure, in particular, a dependence of the measured bone area (BA) on the bone mineral content (BMC). Results of spine bone mineral measurements taken at intervals with two DXA scanners, a Hologic QDR 1000W, and a Norland XR 26 HS, were examined. There was a consistent correlation between changes in BA and in BMC, with a slope of approximately 0.25 when expressed as percentages. A real change of BA of the magnitude observed is not feasible. There were no differences among the correlations for different instruments, genders, ages, or weight changes. There would appear to be an underestimation of changes in bone mineral density (BMD), but there is a possibility that some of the anomaly is manifested as an overestimation of a change in BMC. Phantom measurements were undertaken with the DXA scanners mentioned above and with a Lunar DPX. The phantoms consisted of simulations of the spine cut from aluminium sheet, so that the effective BMD could be varied. The dependence of the measured BA on BMC varied with the phantom outline, particularly the thickness of the transverse processes. Evidence was obtained of both an underestimate of BMD changes and an overestimate of BMC changes. There are errors in measuring spine changes, but these do not seem to be as serious as a previous report suggests for the Hologic scanner and are not likely to lead to misinterpretation of results. Received: 17 June 1997 / Accepted: 23 January 1998     

Bone Density of the Spine and Femur in Adult White Females

We measured bone mineral density (BMD in g/cm²) of the spine (L2-L4) and femur (four regions) in 1472 and 1487 cases, respectively, of ambulatory white women ages 20–79 years in the USA. A DPX densitometer was used in a mobile setting. The BMD values for women up to 69 years corresponded closely with published values for the USA, the UK, and northern Europe; our values were somewhat lower than those from other studies only in women over 70 years. The USA data were combined with data from Europe to give reference curves on about 12,000 subjects. Decreases of BMD with age in women below 50 years were much smaller than in older women (0.2% versus 0.6–1.0% per year). Femoral bone decreased from the neck region, but not the trochanter with age; the decrease of total femur BMD with age was due to loss from the former region. Loss of bone mineral content (BMC in g) from the femur neck and total femur region did not accelerate until after age 50 years, much like the spine. The apparent decrease of BMD in these regions that begins about age 40 actually is due to an increase of bone area. About 20% of USA women aged 50–79 years had BMD levels for the lumbar spine, or for the femur neck, more than −2.5 SD below the average values in young adult women 20–39 years old. Body weight had several times more impact on BMD than height, and in fact, a change of 1 kg in postmenopausal women was commensurate with the effect of a 1-year change in age. Subjects in the lowest quartile of body weight had T-scores that were 1 SD below those in the highest quartile. Received: 10 September 1998 / Accepted: 15 December 1998     

Administration of a Glucocorticoid With Depot Effect Counteracts the Stimulating Effect of Growth Hormone on Cancellous and Cortical Bone of the Vertebral Body in Rats

Our earlier studies have shown that growth hormone administration could not counteract decreased longitudinal growth and cortical osteopenia of rat femora induced by a glucocorticoid with depot effect. In the present study we examined the effects of glucocorticoid on vertebral bone as well as the effect of growth hormone on vertebral bone in young growing animals also given glucocorticoid injections. Five groups of female rats (3 1/2 months) were treated for 80 days as follows: (1) saline, (2) prednisolone: Delcortol 5 mg/kg/day, (3) growth hormone: 5 mg/kg/day, (4) prednisolone and growth hormone, (5) food restriction. Vertebral dimensions, histomorphometry, and mechanical competence of the vertebral bone were examined. Growth hormone administration increased body weight, vertebral height, cross-sectional area, and volume. The compressive strength of the L₄-corpus cylinder was also increased due to an increase in cancellous bone volume and an increase in the area of cortical bone surrounding the vertebral body. Glucocorticoid administration decreased body weight, height, and volume of the intact vertebrae. Histological examination revealed that glucocorticoid administration decreased the area of cortical bone surrounding the vertebral body but had no effect on the cancellous bone volume. No effect of glucocorticoid administration on mechanical strength of the L₄ corpus cylinder could be detected. In agreement with our findings in cortical bone, we found no effect of growth hormone on vertebral bone when given to animals also receiving glucocorticoid injections. Growth hormone increases longitudinal growth, cortical and cancellous bone mass, and mechanical competence of the vertebral body. Glucocorticoid administration decreases longitudinal growth of the vertebrae and cortical bone mass without affecting cancellous bone mass of the vertebral body. Despite this, administration of a glucocorticoid with depot effect totally inhibits the effect of growth hormone on vertebral bone. Received: 12 March 1997 / Accepted: 14 November 1997     

Prophylactic Effects of 1,24,25-Trihydroxyvitamin D3 on Ovariectomy-Induced Cancellous Bone Loss in the Rat

Vitamin D metabolites can prevent estrogen depletion-induced bone loss in ovariectomized (OVX) rats. In this study, we investigated the bone-sparing effects of oral 1α,24R,25-trihydroxyvitamin D₃ (1,24,25(OH)₃D₃) in a wide dose range in aged OVX rats. Fifty-three female Fischer-344 rats (6 months old, 170 g BW) were either ovariectomized or sham-operated (SHAM). Eight rats served as baseline controls. Groups of OVX rats (n= 7–8 each) received vehicle alone or graded oral doses of 1,24,25(OH)₃D₃ (0.05, 0.1, 0.2, and 0.3 μg/kg BW/day), starting five days after surgery. Urine and blood samples were collected one, two, three, and four months after surgery. Serum samples were analyzed for total calcium and alkaline phosphatase. Calcium, hydroxyproline, and collagen crosslinks (HPLC) were determined in urine. After fluorochrome double labeling, the rats were sacrificed four months postsurgery and the first lumbar vertebrae and the proximal tibiae were processed undecalcified for bone histomorphometry. Ovariectomy induced a 28% and a 69% reduction in vertebral and tibial cancellous bone area, respectively. Osteopenia in OVX rats was associated with increased histomorphometric and biochemical indices of bone turnover. The administration of 1,24,25(OH)₃D₃ to OVX rats dose-dependently increased vertebral and tibial cancellous bone mass, serum calcium, and urinary calcium excretion, and reduced histomorphometric and biochemical indices of bone resorption. 1,24,25(OH)₃D₃ at doses of 0.2 and 0.3 μg/kg/day produced strong anabolic effects, especially on vertebral cancellous bone in OVX rats, and increased mineral apposition rate and wall width of completed remodeling units relative to vehicle-treated OVX rats. Even at high doses, 1,24,25(OH)₃D₃ did not impair bone mineralization. We conclude that oral administration of 1,24,25(OH)₃D₃ can effectively prevent estrogen depletion-induced cancellous bone osteopenia in the aged OVX rat model. The therapeutic window for 1,24,25(OH)₃D₃ in OVX rats, however, is also narrow, comparable to that for calcitriol. Received: 29 March 1996 / Accepted: 23 September 1996     

Age-Related Cancellous Bone Loss in the Proximal Femur of Caucasian Females

The purpose of this investigation was to directly define the age-related intrafemoral variations in cancellous bone density, bone mineralization and rate of bone loss in a cadaveric population of Caucasian female femoral necks and trochanters. Forty-three Caucasian female femora were obtained and divided into premenopausal, postmenopausal and elderly age groups. The neck and trochanter were removed, and cores of cancellous bone were taken from the superior, middle and inferior regions; volume fraction and ash fraction were determined for each core. The cancellous bone volume fraction of the neck was significantly greater than that of the trochanter, as was that of the inferior region of the neck compared with the superior and middle regions at all age groups (p<0.05). The mean neck/trochanter and neck inferior/superior volume fraction ratios did not change with age; however, the variance increased with age (p<0.001). This increasing variability with age suggests that there may be a subpopulation of individuals within the elderly Caucasian population with a significantly different intrafemoral bone density distribution than was present prior to menopause. This study identified no mineralization changes with age in the cancellous bone of the proximal femur (p>0.05). The influence of increased neck/trochanter and neck inferior/superior ratios on femoral neck integrity and fracture prediction is of interest and requires further investigation. Received: 8 April 1999 / Accepted: 18 October 1999     

Normal Data for Lumbar Spine Bone Mineral Content in Healthy Chinese Men

The aim of this study was to evaluate the influence of age on bone mineral density (BMD) of the lumbar spine for healthy Chinese men. In 430 healthy Chinese men (ages 20–92 years) living on Taiwan, BMD at the level of the 2nd to 4th lumbar vertebraes (L2–L4) was determined with a commercial dual-energy X-ray absorptiometer (DXA). Our study found that the peak BMD value of lumbar spines of healthy Chinese men was 1.056 ± 0.127 g/cm² which occurs from age 20 to 29. The results show that a linear correlation between the age and BMD of lumbar vertebraes for healthy Chinese is notable. Only slight decreases of BMD values in the different age groups are found. In comparison with the normal data of white men and Asian men from Japan and Korea, the mean BMD values of lumbar spines of Chinese men seem to be lower than those of the white, Japanese, and Korean men of the same ages. Our findings indicate that the influence of age and ethnicity may exist in the BMD values for healthy Chinese males. Received: 15 October 1996 / 3 January 1997     

Cytokine Production and Bone Mineral Density at the Lumbar Spine and Femoral Neck in Premenopausal Women

Cytokines such as interleukin-1 (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) can influence both bone resorption and bone formation. The objective of this cross-sectional study was to examine the relationship between cytokine production by peripheral blood mononuclear cells (PBMC) and bone mineral density (BMD); the annual rate of change in BMD was examined. Subjects participating in a randomized clinical trial entitled the Women's Healthy Lifestyle Project in Allegheny County, Pennsylvania were used. They included 50 healthy premenopausal women, aged 45–52 years, who had regular menses within the past 3 months and were not on replacement estrogens. Dual-energy X-ray absorptiometry measurements at the AP lumbar spine and femoral neck were made at baseline and at the first annual exam using a Hologic QDR 2000 densitometer. Cytokine production of IL-1β, IL-6, and TNF-α by PBMC was measured at the annual exam. The median values for stimulated cytokine production by PBMC were 3.92 ng/ml, 31.3 ng/ml, and 1.05 ng/ml, for IL-1β, IL-6, and TNF-α, respectively. There were modest correlations between cytokine production and cross-sectional BMD, ranging from r =−0.30 to r =−0.13. Trends of greater spinal bone loss were observed in women with ``high' (≥75th percentile) cytokine production of stimulated IL-1β and IL-6 (IL-1β: ``high' =−1.56% ± 0.70 versus ``low' (<75th percentile) =−0.56% ± 0.35, P= 0.21). In contrast, greater annual gains in femoral neck BMD were observed in those with high cytokine production of IL-1β and IL-6 (IL-1β: high = 3.39% ± 1.16 versus low =−0.85 ± 0.58, P= 0.002). There was no association between stimulated TNF production and annual change in BMD. In this population of healthy premenopausal women, the relationship between cytokine production by PBMC and the rate of change in BMD was significantly different for the lumbar spine and femoral neck, possibly reflecting differences in the proportion of trabecular and cortical bone at these sites. Received: 5 February 1997 / Accepted: 11 May 1998     

Bone Mineral Density and Turnover Following Forelimb Immobilization and Recovery in Young Adult Dogs

The purpose of this experiment was to study changes in bone mass, structure, and turnover in the canine forelimb after unilateral immobilization and recovery. The right forelimbs of 14 adult mongrel dogs were immobilized for 16 weeks. Six dogs served as controls. Seven immobilized and three control dogs were euthanized at the end of the immobilization period. Recovery consisted of 16 weeks of kennel confinement followed by 16 weeks of treadmill exercise. Seven once-immobilized and three control dogs were euthanized at the end of the recovery period. Bone mineral density of both the proximal (PBMD) and central (CBMD) radius was determined by dual X-ray absorptiometry. Standard histomorphometric endpoints for bone mass and turnover were determined in the cancellous bone of the proximal radius. After immobilization, PBMD, CBMD, and trabecular thickness were lower in the immobilized limb than in either the contralateral or control limbs (P < 0.05). Only CBMD remained significantly lower (P < 0.05) after recovery. At the end of immobilization, bone formation endpoints were significantly higher in the immobilized limb than both the contralateral and control limbs. Bone turnover was also significantly lower in the contralateral limb than in the immobilized and control limbs. After recovery, all differences in bone turnover had resolved. Immobilization of 16 weeks duration caused an elevation in cancellous bone formation rate and reduced bone density in both cortical and cancellous bone. After 32 weeks of recovery, turnover abnormalities disappeared, cancellous bone normalized, but cortical bone mass remained low. Recovery of cortical bone from immobilization takes longer than recovery of cancellous bone. Received: 28 January 1996 / Accepted: 3 May 1996     

Effect of Estrogen Deficiency on Cancellous and Cortical Bone Structure and Strength of the Femoral Neck in Rats

Eighty mature Sprague-Dawley rats were weight matched before ovariectomy (Ovx) or Sham surgery (Sham). Sham rats had free access to food and water throughout the experiment, whereas Ovx rats were kept on the pair-fed diet. Rats were euthanized at 4, 8, and 12 weeks after surgery, and had received fluorochrome bone markers at 9 and 2 days prior to euthanasia. In addition 10 rats were euthanized at the time of surgery serving as baseline controls. All rats were also scanned for body composition and bone mineral parameters by DEXA before surgery and euthanasia. Left proximal femurs (femoral necks) were used for bone histomorphometry, whereas right femurs were used for in vitro DEXA measurements and mechanical testing. Despite pair-feeding, ovariectomized rats had increased body weights and fat body mass, whereas the percent lean body mass steadily declined throughout the experiment. Mineral density of the whole femur and femoral neck was significantly higher in the Sham rats relative to Ovx animals. Ovariectomy reduced trabecular number and thickness, and increased trabecular separation and bone marrow space at the femoral midneck location. The structure of the remaining trabeculae was dramatically changed toward simpler struts as revealed by nodal analyses. Cortical thickness in Ovx rats was reduced because of the high endocortical resorption, which, in addition to cancellous bone resorption, resulted in fewer endocortico-trabecular connections. Femoral necks obtained from ovariectomized rats had reduced strength and were less stiff relative to controls. Because of the enormous clinical significance of the proximal femur for osteoporosis in humans, and the opportunity for studying bone BMD, mass, structure, and strength at the same skeletal location, the femoral neck appears superior to other skeletal sites routinely used for bone histomorphometry or mechanical testing in the Ovx rat model. Received: 25 September 1996 / Accepted: 24 March 1997     

Orchiectomy Increases Bone Marrow Interleukin-6 Levels in Mice

Interleukin-6 (IL-6) appears to be an important factor in disease states associated with bone resorption. There is both in vitro and in vivo evidence supporting the fact that androgens down-regulate interleukin-6 production. These observations, in combination with the fact that osteoblasts and bone marrow stromal cells produce IL-6, led us to hypothesize that orchiectomy-induced androgen loss will result in increased IL-6 expression in the bone microenvironment. To prove our hypothesis we assessed the effect of orchiectomy on IL-6 protein and mRNA expression in bone marrow and spleen. We found that orchiectomy was associated with increased serum IL-6 levels at 3 and 28 days postsurgery. Phorbol ester-stimulated IL-6 levels were also higher in supernatants from bone marrow and spleen cell cultures from orchiectomized mice compared with unoperated or sham-operated mice. Additionally, we found that steady state IL-6 mRNA levels were increased in bone marrow but not spleen cells. Finally, we found that orchiectomized mice had splenomegaly and increased bone marrow cellularity. Histopathology of the spleen revealed lymphoid hyperplasia accompanied by a marked mononuclear cell infiltration of the red pulp. We conclude that orchiectomy induces IL-6 expression in the bone marrow. These findings suggest that endocrine and cytokine interactions contribute to bone pathophysiology. Received: 17 January 1997 / Accepted: 2 September 1997     

Dissimilar Spine and Femoral Z-Scores in Premenopausal Women

The purpose of this study was to determine if differences exist in premenopausal women between z-scores for lumbar spine and proximal femoral bone mineral densities (BMD). Participants were 237 women ranging in age from 20 to 45 years. BMDs of the lumbar spine and proximal femur (femoral neck, Ward's area, and trochanter) were assessed using dual-energy X-ray absorptiometry (Lunar DPX). Mean (±SD) age, height, and weight of the participants were 29.4 ± 6.9 years, 164.4 ± 6.1 cm, and 64.9 ± 12.1 kg, respectively. Lumbar spine BMD and BMD at the femoral neck, Ward's area, and trochanter were significantly correlated with large SEEs (r = 0.59–0.65; SEE = 0.09–0.11). No positive correlation with age and BMD at any site was seen in this population but a significant negative correlation with age was seen in the proximal femur beginning at age 30. Twenty to 24% of the 20–29-year-olds exhibited a difference in z-scores of greater than 1 between the spine and sites in the proximal femur. This percentage increased to 32–46% in the 30–45-year-olds but the nature of the observed differences changed. The differences in spine and proximal femoral z-scores that are seen in the older age group appear to be the result of the earlier onset of bone loss in the proximal femur rather than an initial difference in peak bone mass which has been maintained. Received: 28 August 1996 / Accepted: 25 April 1997