Growth hormone and bone health

Growth hormone (GH) and insulin-like growth factor-I have major effects on growth plate chondrocytes and all bone cells. Untreated childhood-onset GH deficiency (GHD) markedly impairs linear growth as well as three-dimensional bone size. Adult peak bone mass is therefore about 50% that of adults with normal height. This is mainly an effect on bone volume, whereas true bone mineral density (BMD; g/cm(3)) is virtually normal, as demonstrated in a large cohort of untreated Russian adults with childhood-onset GHD. The prevalence of fractures in these untreated childhood-onset GHD adults was, however, markedly and significantly increased in comparison with normal Russian adults. This clearly indicates that bone mass and bone size matter more than true bone density. Adequate treatment with GH can largely correct bone size and in several studies also bone mass, but it usually requires more than 5 years of continuous treatment. Adult-onset GHD decreases bone turnover and results in a mild deficit, generally between -0.5 and -1.0 z-score, in bone mineral content and BMD of the lumbar spine, radius and femoral neck. Cross-sectional surveys and the KIMS data suggest an increased incidence of fractures. GH replacement therapy increases bone turnover. The three controlled studies with follow-up periods of 18 and 24 months demonstrated a modest increase in BMD of the lumbar spine and femoral neck in male adults with adult-onset GHD, whereas no significant changes in BMD were observed in women. GHD, whether childhood- or adult-onset, impairs bone mass and strength. Appropriate substitution therapy can largely correct these deficiencies if given over a prolonged period. GH therapy for other bone disorders not associated with primary GHD needs further study but may well be beneficial because of its positive effects on the bone remodelling cycle.     

Influence of growth hormone on accretion of bone mass

Growth hormone (GH) exerts important influences on bone metabolism during lifespan. During childhood, GH is a major determinant of acquisition of bone mass and in adult life, GH partly determines the rate of bone remodelling and therefore influences maintenance of bone mineral density (BMD). Insights into the importance of GH in these respects may be obtained by studies of BMD and indices of bone remodelling in GH deficiency (GHD) of adult-onset and childhood-onset. Adult-onset GHD, usually accompanied by other features of hypopituitarism, may be associated with osteopenia and an increased fracture risk. Postulated mechanisms include GHD and gonadal steroid deficiency of unknown duration; glucocorticoid and thyroxine replacement do not appear to exert a major role. GH replacement in adult-onset GHD results in an early increment in indices of bone remodelling which persists for up to 5 years; BMD increases by 0.5-1.0 SD in males and stabilizes in females over this time period. In adolescents with GHD who traditionally discontinue GH at completion of linear growth, BMD is substantially lower than peak bone mass for a young adult population. Studies addressing the effects of continuation of GH after achievement of final height are currently underway and will provide insights into the possible need to continue GH into adult life. Such studies may confirm a role for GH in promoting continued accrual of bone mass and thereby demonstrate that cessation of GH at achievement of final height, by limiting peak bone mass, may predispose to clinically significant osteoporosis in later life. In addition to the potential importance of GH for achievement of peak bone mass, there may be a superimposed accelerated loss of BMD with advancing age similar to the situation observed in adult-onset GHD. To date, this has been difficult to assess in adult GHD of childhood-onset because the relative contributions of low peak bone mass and increased loss of bone in later life could not be distinguished.     

Effects of growth hormone replacement therapy on bone markers and bone mineral density in growth hormone-deficient adults

During the 1990s, interest in the effects of growth hormone deficiency (GHD) in adults increased, and several studies were performed to evaluate the effects of growth hormone (GH) substitution therapy in these patients. Because adults with GHD have reduced bone mineral density (BMD) and an increased risk of fractures, the effects of GH replacement therapy on bone metabolism have been evaluated in long-term studies. A universal finding is that the serum and urinary levels of biochemical bone markers increase during GH substitution therapy, and these increases are dose dependent. After years of GH substitution therapy, the levels of biochemical bone markers remain elevated, according to some studies, whereas other studies report that these levels return to baseline. BMD of the spine, hip and forearm increase after 18-24 months of treatment. Bone mineral content (BMC) increases to a greater extent than BMD, because the areal projection of bone also increases. This difference could be caused by increased periosteal bone formation, but a measurement artefact resulting from the use of dual-energy X-ray absorptiometry cannot be excluded as a possible explanation. One study of GH-deficient adults found that, after 33 months of GH treatment, BMD and BMC increased to a greater extent in men with GHD than in women. There is also a gender difference in the increases in serum levels of insulin-like growth factor I and biochemical bone markers during GH treatment. The reason for these findings is unknown, and the role of sex steroids in determining the response to GH therapy remains to be fully elucidated.     

Impact of growth hormone status on body composition and the skeleton

Severe growth hormone (GH) deficiency (GHD) induces a well-defined clinical entity encompassing, amongst the most reported features, abnormalities of body composition, in particular increased fat mass, especially truncal, and reduced lean body mass. The results from virtually all treatment studies are in agreement that GH replacement improves the body composition profile of GHD patients by increasing lean body mass and reducing fat mass. More recently, the observations have been extended to adults with partial GHD, defined by a peak GH response to insulin-induced hypoglycaemia of 3-7 microg/l. These patients exhibit abnormalities of body composition similar in nature to those described in adults with severe GHD; these include an increase in total fat mass of around 3.5 kg and a reduction of lean body mass of around 5.5 kg. The increase in fat mass is predominantly distributed within the trunk. The degree of abnormality of body composition is intermediate between that of healthy subjects and that of adults with GHD. The impact of GH replacement on body composition in adults with GH insufficiency, although predictable, has not been formally documented. The skeleton is another biological endpoint affected by GH status: in adults with severe GHD, low bone mass has been reported using dual energy x-ray absorptiometry (DEXA) and other quantitative methodologies. The importance of low bone mass, in any clinical setting, is as a surrogate marker for the future risk of fracture. Several retrospective studies have documented an increased prevalence of fractures in untreated GHD adults. Hypopituitary adults with severe GHD have reduced markers of bone turnover which normalize with GH replacement, indicating that GH, directly or via induction of insulin-like growth factor-I, is intimately involved in skeletal modelling. Whilst the evidence that GH plays an important role in the acquisition of bone mass during adolescence and early adult life is impressive, the impact of GHD acquired later in adulthood is less clear. Recently we examined the relationship between bone mineral density (BMD) and age in 125 untreated adults with severe GHD using DEXA. A significant positive correlation was observed between BMD (z-scores) and age at all skeletal sites studied. Overall, few patients, except those aged less than 30 years, had significantly reduced bone mass (i.e. a BMD z-score of less than -2); correction of BMD to provide a pseudo-volumetric measure of BMD suggested that reduced stature of the younger patients may explain, at least in part, this higher frequency of subnormal BMD z-scores. Despite normal BMD, however, an increase in fracture prevalence may still be observed in elderly GHD adults as a consequence of increased falls related to muscle weakness and visual field defects.     

Long-term effects of growth hormone therapy on bone mineral density,body composition,and serum lipid levels in growth hormone deficient children: a 6-year follow-up study

AIM: To study the effects of growth hormone (GH) deficiency (GHD) and GH replacement therapy (GHRx) on bone mineral density (BMD) and body composition. METHODS: 59 GHD children participated (age range 0.4-16.9 years); the follow-up period was 6 years. Lumbar spine BMD (BMD(LS)), total-body BMD (BMD(TB)), and body composition were measured prospectively using dual-energy X-ray absorptiometry. RESULTS: Mean BMD(LS )and BMD(TB) were significantly reduced at the time of the diagnosis. The bone mineral apparent density of the lumbar spine (BMAD(LS)) was reduced to a lesser degree. The BMAD(LS) increased to normal values after 1 year; BMD(LS) and BMD(TB) normalized 1 year later. At the time of the diagnosis, the lean body mass was reduced and steadily increased during GHRx. Percentage of body fat was increased at baseline and normalized within 6 months. The severity of GHD was not associated with the BMD at diagnosis or the response to GHRx. CONCLUSION: Areal BMD(LS) and BMD(TB) and, to a lesser extent, BMAD(LS) are decreased in GHD children, but normalize within 1-2 years.     

Relation of bone mineral density and content to mineral content and density of the fat-free mass.

Differences in the mineral fraction of the fat-free mass (M(FFM)) and in the density of the FFM (D(FFM)) are often inferred from measures of bone mineral content (BMC) or bone mineral density (BMD). We studied the relation of BMC and BMD to the M(FFM) and D(FFM) in a heterogeneous sample of 216 young men (n = 115) and women (n = 101), which included whites (n = 155) and blacks (n = 61) and collegiate athletes ( n = 132) and nonathletes (n = 84). Whole body BMC and BMD were determined by dual-energy X-ray absorptiometry (DXA; Hologic QDR-1000W, enhanced whole body analysis software, version 5.71). FFM was estimated using a four-component model from measures of body density by hydrostatic weighing, body water by deuterium dilution, and bone mineral by DXA. There was no significant relation of BMD to M(FFM) (r = 0.01) or D(FFM) (r = -0.06) or of BMC to M(FFM) (r = -0.11) and a significant, weak negative relation of BMC to D(FFM) (r = -0.14, P = 0.04) in all subjects. Significant low to moderate relationships of BMD or BMC to M(FFM) or D(FFM) were found within some gender-race-athletic status subgroups or when the effects of gender, race, and athletic status were held constant using multiple regression, but BMD and BMC explained only 10-17% of the variance in M(FFM) and 0-2% of the variance in D(FFM) in addition to that explained by the demographic variables. We conclude that there is not a significant positive relation of BMD and BMC to M(FFM) or D(FFM) in young adults and that BMC and BMD should not be used to infer differences in M(FFM) or D(FFM).     

Calcium supplementation increases bone mass in GH-deficient prepubertal children during GH replacement

BACKGROUND/AIMS: Since GH plays an important role in bone mineralization, and several studies demonstrated the positive influence of a higher calcium intake on bone mass, we studied the effect of calcium supplementation in GHD children during GH therapy. METHODS: 28 prepubertal GHD children, 5.0-9.9 years old, were assigned to two groups: group A (n = 14; 7 females) treated with GH, and group B (n = 14; 7 females) treated with GH + calcium gluconolactate and carbonate (1 g calcium/day per os). Auxological parameters, total bone mineral content (TBMC) and density (TBMD), leg BMC and BMD, lumbar BMD, fat mass (FM) and lean tissue mass (LTM), blood 25-hydroxyvitamin D (25-OHD), parathyroid hormone (PTH), osteocalcin (OC) and urinary N-terminal telopeptide of type I collagen (NTx) were determined at the start of therapy and after 1 and 2 years of treatment. RESULTS: During the 2 years of the study, TBMC, TBMD, leg BMC and BMD (but not lumbar BMD) increased in both groups of patients, however after 2 years of treatment they were significantly higher in the calcium-supplemented group B than in group A (p < 0.05, for all parameters). At the start of therapy, in both groups of patients percentage FM was higher and total and leg LTM lower than in controls (p < 0.05 for each parameter). Thereafter, FM decreased and LTM increased and after 2 years they were both different from baseline (p < 0.05). After 2 years of treatment, leg BMC and BMD were more positively correlated with regional leg LTM in patients of group B (r = 0.834 and r = 0.827, respectively; p < 0.001) than in patients of group A (r = 0.617 and r = 0.637, respectively; p < 0.05). 25-OHD and PTH levels were in the normal range in all patients at the start and during treatment. OC levels were lower and urinary NTx levels higher in patients than in controls (p < 0.05 for both parameters), either at the start and after 1 year of treatment. After 2 years of treatment, OC levels were significantly higher than at the start of the study (p < 0.05) in both groups of patients, but they were higher in group B than in group A (p < 0.05); on the contrary, urinary Ntx levels were lower in group B than in group A (p < 0.05). CONCLUSION: In GHD children, treated with GH, calcium supplementation improved bone mass; it may aid in reaching better peak bone mass and in protecting weight-bearing bones, usually completed in childhood to maximum levels, from risk of osteoporosis and fractures later in life.     

Reduced bone mineral density and radial bone growth in young rabbits treated with dexamethasone eye drops

OBJECTIVE: To investigate the effect of dexamethasone eye drops on bone metabolism in newborn rabbits. METHODS: Thirty-four 3-week-old rabbits had unilateral clear lens extraction and were randomized into three groups. Postoperatively, group 1 received high-dose and group 2 low-dose dexamethasone eye drops (average doses 0.27 and 0.10 mg/kg body weight/day, respectively). These rabbits also received a postoperative subconjunctival injection of betamethasone. Group 3 (control) received vehicle eye drops only. After 8 weeks of treatment, all animals were killed and the left femurs were isolated and subjected to peripheral quantitative computerized tomography (pQCT) and dual X-ray absorptiometry (DXA) analyses. RESULTS: DXA showed that rabbits treated with either a high or low dose of dexamethasone eye drops had significantly reduced areal bone mineral density (BMD), area and total bone mineral content (BMC) of the femur. Measurements with pQCT demonstrated a dose-dependent reduction in cortical BMC, cortical volumetric BMD and cortical area. These effects were associated with an inhibition of radial femur growth, cortical thickness and periosteal and endosteal circumferences. CONCLUSION: Dexamethasone eye drops have systemic effects affecting several bone parameters in young rabbits. Any long-term systemic effects of ocular glucocorticoids need to be further studied.     

Radial bone mineral content of normal Japanese infants and prepubertal children: influence of age,sex and body size

The present study was performed to measure appendicular bone mass of Japanese infants and children, and to assess the influence of age, sex and body size on bone mass during the period of bone growth. The bone mineral content (BMC) and bone width (BW) at the distal third of the radius were measured by single photon absorptiometry (SPA) in 229 healthy Japanese infants and children aged 0–12 years, and the BMC/BW ratio was calculated to give the bone mineral density (BMD). BMC and BW increased with age until 2 years, while BMD did not obviously change until 2 years. After 2 years of age, the overall effect of aging appeared more prominent in BMC and BMD than in BW. There were no significant differences in BMC, BW and BMD between males and females aged 0–12 years. Age, body height, and body weight were strongly correlated with three parameters of bone mass (BMC, BW, and BMD). Among the three parameters of bone mass, BMC showed the highest Pearson coefficient of correlation with age (r = 0.955), body height (r = 0.957) and body weight (r = 0.966), as compared with BW and BMD. The present cross-sectional study provides normative data of the appendicular bone mass in healthy Japanese children, which may serve as a standard for assessment of bone mineralization in Japanese infants and children with medical problems.     

Disproportional skeletal growth and markedly decreased bone mineral content in growth hormone receptor -/- mice

Growth hormone (GH) is important for skeletal growth as well as for a normal bone metabolism in adults. The skeletal growth and adult bone metabolism was studied in mice with an inactivated growth hormone receptor (GHR) gene. The lengths of femur, tibia, and crown-rump were, as expected, decreased in GHR-/- mice. Unexpectedly, GHR-/- mice displayed disproportional skeletal growth reflected by decreased femur/crown-rump and femur/tibia ratios. GHR-/- mice demonstrated decreased width of the growth plates in the long bones and disturbed ossification of the proximal tibial epiphysis. Furthermore, the area bone mineral density (BMD) as well as the bone mineral content (BMC)/body weight were markedly decreased in GHR-/- mice. The decrease in BMC in GHR-/- mice was not due to decreased trabecular volumetric BMD but to a decreased cross-sectional cortical bone area In conclusion, GHR-/- mice demonstrate disproportional skeletal growth and markedly decreased bone mineral content.     

Moderate Zinc Supplementation During Prolonged Steroid Therapy Exacerbates Bone Loss in Rats

The present study was conducted to understand the influence of zinc on bone mineral metabolism in prednisolone-treated rats. Disturbance in bone mineral metabolism was induced in rats by subjecting them to prednisolone treatment for a period of 8 weeks. Female rats aged 6–8 weeks weighing 150 to 200 g were divided into four treatment groups, viz., normal control, prednisolone-treated (40 mg/kg body weight orally, thrice a week), zinc-treated (227 mg/L in drinking water, daily), and combined prednisolone?+?zinc-treated groups. Parameters such as changes in mineral levels in the bone and serum, bone mineral density (BMD), bone mineral content (BMC), and bone 99m-technetium-labeled methylene diphosphonate (^99mTc-MDP) uptake were studied in various treatment groups. Prednisolone treatment caused an appreciable decrease in calcium levels both in the bone and serum and also in bone dry weight, BMC, and BMD in rats. Prednisolone-treated rats when supplemented with zinc showed further reduction in calcium levels, bone dry weight, BMD, and BMC. The study therefore revealed that moderate intake of zinc as a nutritional supplement during steroid therapy could enhance calcium deficiency in the body and accelerate bone loss.     

Validation of a dual energy X-ray absorptiometer: measurement of bone mass and soft tissue composition

We investigated the reproducibility of total and regional body composition measurements performed on a dual energy X-ray absorptiometer (DXA). A group of 38 women aged 21–81 (mean 52. 4) years was scanned twice with repositioning to determine intra-observer reproducibility of measurements of bone mineral density (BMD, g · cm⁻²), bone mineral content (BMC, g), lean mass (LM, kg) and fat mass (FM, kg) of the total body and of the major subregions of the body. In addition, the ability of the DXA machine to detect changes in LM and FM (simulated by placing 11.1 and 22.3 kg porcine lard on the body of 11 subjects) was examined. Coefficients of variations calculated from the root mean square averages of individual standard deviations were as follows (BMD, BMC, FM, LM): 1.4%, 1.1%, 1.4%, 1.7% (total body), 2.2%, 2.1%,-,- (head), 2.8%, 2.8%, 2.0%, 2.2% (trunk), 3.6%, 3.9%, 4.0%, 4.9% (arms), 2.7%, 1.3%, 2.6%, 2.8% (legs). Percentage fat (%fat) of exogenous lard was 81.3 (SD 3.5)% as assessed by the absorptiometer which corresponded well with the result of chemical analysis (82.8%). Estimated %fat of exogenous lard was not influenced by initial body mass or percentage body fat. Percentages of expected mean values with 11.1 kg lard placed on the body were 99.9 (SD 0.3) for body mass, 100.5 (SD 2.1) for LM, and 99.5 (SD 3.5) for FM. BMD was overestimated by 3.2% (P < 0.005) with 11.1 kg lard on the body. BMD as well as BMC increased significantly with 22.3␣kg lard on the body (P < 0.005). The results showed that BMD, BMC, LM, and FM of the total body were precisely estimated by the DXA machine used. Regional measurements were less precise. Changes in total body soft tissue composition were precisely and accurately estimated. The lard placed on the body falsely affected BMD and BMC measurements. Changes in body mass could have a similar effect. Accepted: 6 January 1997     

Accuracy and precision of dual-energy X-ray absorptiometry for body composition measurements in rhesus monkeys

Accuracy of body composition measurements by dual-energy X-ray absorptiometry (DXA) was compared with direct chemical analysis in 10 adult rhesus monkeys. DXA was highly correlated (r-values > 0.95) with direct analyses of body fat mass (FM), lean mass (LM) and lumbar spine bone mineral content (BMC). DXA measurements of total body BMC were not as strongly correlated (r-value = 0.58) with total carcass ash content. DXA measurements of body FM, LM and lumbar spine BMC were not different from data obtained by direct analyses (P-values > 0.30). In contrast, DXA determinations of total BMC (TBMC) averaged 15%, less than total carcass ash measurements (P = 0.002). In conclusion, this study confirms the accurate measurement of fat and lean tissue mass by DXA in rhesus monkeys. DXA also accurately measured lumbar spine BMC but underestimated total body BMC as compared with carcass ash determinations.     

Bone markers and bone mineral density during growth hormone treatment in children with growth hormone deficiency

Growth hormone (GH) has a positive impact on muscle mass, growth and bone formation. It is known to interact with the bone-forming unit, with well-documented increases in markers of bone formation and bone resorption within weeks of the start of GH therapy. These changes relate significantly to short-term growth rate, but it is not evident that they predict long-term response to GH therapy. The consequences of GH deficiency (GHD) and GH replacement therapy on bone mineral density (BMD) have been difficult to interpret in children because of the dependency of areal BMD on height and weight. Some studies have tried to overcome this problem by calculating volumetric BMD, but results are conflicting. The attainment of a normal peak bone mass in an individual is considered important for the future prevention of osteoporosis. From the limited data available, it appears difficult to normalize bone mass totally in GH-deficient individuals, despite GH treatment for long periods. Studies to date examining the interaction between GH and bone have included only small numbers of individuals, making it difficult to interpret the study findings. It is hoped that these issues can be clarified in future research by the direct measurement of bone density (using quantitative computer tomography). Mineralization is only one facet of bone strength, however; other important components (e.g. bone structure and geometry) should be addressed in future paediatric studies. Future studies could also address the importance of the degree of GHD in childhood; how GH dose and insulin-like growth factor-I levels achieved during therapy relate to the final outcome; whether or not the continuation of GH therapy after the attainment of final height may further enhance bone mass; whether the timing and dose of other treatments (e.g. sex hormone replacement therapy) are critical to the outcome; and whether GHD in childhood is associated with an increased risk of fracture.     

The effects of growth hormone on cortical and cancellous bone

Growth hormone (GH) has profound effects on linear bone growth, bone metabolism and bone mass. The GH receptor is found on the cell surface of osteoblasts and osteoclasts, but not on mature osteocytes. In vitro, GH stimulates proliferation, differentiation and extracellular matrix production in osteoblast-like cell lines. GH also stimulates recruitment and bone resorption activity in osteoclast-like cells. GH promotes autocrine/paracrine insulin-like growth factor 1 (IGF-I) production and endocrine (liver-derived) IGF-I production. Some of the GH-induced effects on bone cells can be blocked by IGF-I antibodies, while others cannot. In animal experiments, GH administration increases bone formation and resorption, and enhances cortical bone mass and mechanical strength. When GH induces linear growth, increased cancellous bone volume is seen, but an unaffected cancellous bone volume is found in the absence of linear growth. Patients with acromegaly have increased bone formation and resorption markers. Bone mass results are conflicting because many acromegalics have hypogonadism, but in acromegalics without hypogonadism, increased bone mineral density (BMD) is seen in predominantly cortical bone, and normal BMD in predominantly cancellous bone. Adult patients with growth hormone deficiency have decreased bone mineral content and BMD. GH therapy rapidly increases bone formation and resorption markers. During the first 6-12 months of therapy, declined or unchanged BMD is found in the femoral neck and lumbar spine. All GH trials with a duration of two years or more show enhanced femoral neck and lumbar spine BMD. In osteoporotic patients, GH treatment quickly increases markers for bone formation and resorption. During the first year of treatment, unchanged or decreased BMD values are found, whereas longer treatment periods report enhanced or unchanged BMD values. However, existing trials comprising relatively few patients and limited treatment periods do not allow final conclusions to be drawn regarding the effects of GH on osteoporosis during long-term treatment.     

Cross-sex pattern of bone mineral density in early onset gender identity disorder

Hormonally controlled differences in bone mineral density (BMD) between males and females are well studied. The effects of cross-sex hormones on bone metabolism in patients with early onset gender identity disorder (EO-GID), however, are unclear. We examined BMD, total body fat (TBF) and total lean body mass (TLBM) in patients prior to initiation of sex hormone treatment and during treatment at months 3 and 12. The study included 33 EO-GID patients who were approved for sex reassignment and a control group of 122 healthy Norwegians (males, n=77; females, n=45). Male patients (n=12) received an oral dose of 50 mug ethinylestradiol daily for the first 3 months and 100 mug daily thereafter. Female patients (n=21) received 250 mg testosterone enantate intramuscularly every third week. BMD, TBF and TLBM were estimated using dual energy X-ray absorptiometry (DXA). In male patients, the DXA measurements except TBF were significantly lower compared to their same-sex control group at baseline and did not change during treatment. In female patients, the DXA measurements were slightly higher than in same-sex controls at baseline and also remained unchanged during treatment. In conclusion, this study reports that body composition and bone density of EO-GID patients show less pronounced sex differences compared to controls and that bone density was unaffected by cross-sex hormone treatment.     

Maternal supplementation with dietary arachidonic and docosahexaenoic acids during lactation elevates bone mass in weanling rat and guinea pig offspring even if born small sized

Whether post-natal long chain polyunsaturated fatty acids (LCPUFA) elevates bone mineral content (BMC) of small and normal neonates was studied using pregnant rats and guinea pigs fed a control (C) diet or low protein (LP) diet to induce small neonates followed by C or LCPUFA diets during lactation. Measurements (days 3 and 21 post-partum) included BMC and density (BMD) plus bone metabolism. In rats LP reduced birth weight but at day 21 elevated weight and whole body BMC; LCPUFA enhanced spine BMC, tibia BMC and BMD and whole body BMD. In guinea pig pups, at days 3 and 21, LP reduced weight, whole body and regional BMC and BMD whereas LCPUFA reduced day 3 osteocalcin and elevated day 21 spine BMD. LCPUFA minimized loss of whole body BMC in dams and elevated osteocalcin in sows. LCPUFA during lactation enhances bone in normal and small neonates without compromising maternal bone.     

Is there growth hormone deficiency in prader-willi Syndrome? Six arguments to support the presence of hypothalamic growth hormone deficiency in Prader-Willi syndrome

Prader-Labhart-Willi syndrome (PWS) is the most frequent form of syndromal obesity. Its main features are associated with hypothalamic dysfunction, which has not yet been comprehensively described. The aim of this review is to present arguments to define the presence of genuine growth hormone (GH) deficiency (GHD) in these patients. Decreasing growth velocity despite the onset of obesity, reduced lean body mass in the presence of adiposity, small hands and feet, relatively low insulin-like growth factor-I and low insulin levels, as well as the dramatic effect of GH treatment on growth, support the presence of hypothalamic GHD in PWS. Even though it might be difficult to ultimately prove GHD in PWS because of the obesity-induced counterregulation, the hormonal situation differs from that in simple obesity. The effects of long-term therapies with GH on body composition in these patients are summarized. GH therapy dramatically changes the phenotype of PWS in childhood: height and weight become normal and there is a sustained impact on the net loss of body fat. We conclude that GHD may account for several features of PWS.     

Bone mineralisation of weaned piglets fed a diet free of inorganic phosphorus and supplemented with phytase,as assessed by dual-energy X-ray absorptiometry

Sixteen female piglets (58 d of age, 16.8 ± 0.8 kg body weight [BW]) were assigned to two groups (n = 8) and received until day 100 of age (50.3 ± 1.2 kg BW) ad libitum either a diet with a standard (diet C) or low (diet L) total phosphorus (P) content (5.38 and 4.23 g/kg, respectively). Diet C was supplemented with mineral P (1.15 g/kg) and did not contain microbial phytase. Diet L did not contain any inorganic P but 750 FTU/kg of microbial phytase. Despite these treatments, both diets were composed with the same ingredients. Body mineralisation of each gilt was assessed by determining the bone mineral content (BMC), area bone mineral density (BMD) by the dual-energy X-ray absorptiometry (DXA) at days 58, 72, 86 and 100 of age. Feeding diet L caused a higher P digestibility (p = 0.008) measured from days 72 to 86 of age and at 100 days of age a higher BMC and BMD (p ≤ 0.01). Furthermore, the gilts of group L deposited more minerals in the body than control pigs (by 2.4 g/d, p = 0.008). It was found that BMD and BMC were positively correlated with body lean mass and digestible P intake. The results indicated that, even for very young pigs, the addition of microbial phytase instead of inorganic P increases the amount of digestible P covering the requirements of piglets for proper bone mineralisation. Furthermore, it was proved that the DXA method can be successfully applied to measure body fat and lean mass contents as well as bone mineralisation of growing pigs using the same animals.     

Effect of Group vs. Single Housing on Phenotypic Variance in C57BL/6J Mice

Objective: To determine if group housing affects the variance of body composition parameters in a highly inbred mouse strain. Research Methods and Procedures: Thirty 3‐week‐old male C57BL/6J mice were obtained from the Jackson Laboratory. Fifteen mice were housed individually, and 15 mice were housed in groups of 5/cage. Animals were fed ad libitum and maintained in the same room under a 12:12‐hour light/dark photoperiod at 22 °C for 9 weeks. Animals were killed, and fat mass, soft‐lean tissue mass, bone mineral density (BMD), and bone mineral content (BMC) were determined by DXA. At necropsy, weights of the paired epididymal fat pads, paired retroperitoneal fat pads, right inguinal fat pad, liver, kidneys, paired testes, and seminal vesicles were obtained. Results: Relative to mice housed singly, group‐housed mice showed significantly greater variance in percentage of body fat, testes weight, and BMC. Group‐housed mice tended to show greater variance in liver weights and BMD. Mice housed singly were smaller, had less soft‐lean tissue mass and BMC, and lower BMD when compared with group‐housed mice. Discussion: These results suggest that with respect to body composition parameters, mice housed singly are more similar to one another than are group‐housed mice, most likely because of a reduction in environmental (predominately behavioral/social) effects. Thus, mice housed singly may be more representative of genotypic effects on body composition than group‐housed mice. Whether other inbred strains of mice show similar responses to housing condition is unknown.