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Les personnes polyhandicapées sont très vulnérables sur le plan respiratoire pour de multiples raisons combinées : défaut de développement du parenchyme pulmonaire, troubles neurologiques de la commande respiratoire, étroitesse et rigidité de la cage thoracique, scoliose, inefficacité de la toux… Des problèmes digestifs surajoutés gênent l’efficience ventilatoire, comme les fausses routes alimentaires, le reflux gastro-œsophagien, les surinfections broncho-pulmonaires, les troubles du transit… Ces troubles concourent à une altération globale et insidieuse de l’état général, avec un défaut de corpulence et une plus grande fragilité lors des périodes critiques comme la chirurgie musculo-squelettique de bassin ou du rachis. Les équipes pédiatriques et de rééducation doivent connaître le risque respiratoire des polyhandicapés afin de mettre en place à bon escient, sans restriction ni acharnement, les mesures préventives et thérapeutiques utiles à assurer leur meilleur confort.

Minimal trauma fractures in bone diseases are the result of bone fragility. Rather than considering bone fragility as being the result of a reduced amount of bone, we recognize that bone fragility is the result of changes in the material and structural properties of bone. A better understanding of the contribution of each component of the material composition and structure and how these interact to maintain whole bone strength is obtained by the study of metabolic bone diseases. Disorders of collagen (osteogenesis imperfecta and Paget's disease of bone), mineral content, composition and distribution (fluorosis and osteomalacia); diseases of high remodeling (postmenopausal osteoporosis, hyperparathyroidism, and hyperthyroidism) and low remodeling (osteopetrosis, pycnodysostosis); and other diseases (idiopathic male osteoporosis, corticosteroid-induced osteoporosis) produce abnormalities in the material composition and structure that lead to bone fragility. Observations in patients and in animal models provide insights on the biomechanical consequences of these illnesses and the nature of the qualities of bone that determine its strength.

Exercise during growth results in biologically important increases in bone mineral content (BMC). The aim of this study was to determine whether the effects of loading were site specific and depended on the maturational stage of the region. BMC and humeral dimensions were determined using DXA and magnetic resonance imaging (MRI) of the loaded and nonloaded arms in 47 competitive female tennis players aged 8–17 years. Periosteal (external) cross‐sectional area (CSA), cortical area, medullary area, and the polar second moments of area (IP, mm4) were calculated at the mid and distal sites in the loaded and nonloaded arms. BMC and IPof the humerus were 11–14% greater in the loaded arm than in the nonloaded arm in prepubertal players and did not increase further in peri‐ or postpubertal players despite longer duration of loading (both, p< 0.01). The higher BMC was the result of a 7–11% greater cortical area in the prepubertal players due to greater periosteal than medullary expansion at the midhumerus and a greater periosteal expansion alone at the distal humerus. Loading late in puberty resulted in medullary contraction. Growth and the effects of loading are region and surface specific, with periosteal apposition before puberty accounting for the increase in the bone's resistance to torsion and endocortical contraction contributing late in puberty conferring little increase in resistance to torsion. Increasing the bone's resistance to torsion is achieved by modifying bone shape and mass, not necessarily bone density.

Exercise during growth results in biologically important increases in bone mineral content (BMC). The aim of this study was to determine whether the effects of loading were site specific and depended on the maturational stage of the region. BMC and humeral dimensions were determined using DXA and magnetic resonance imaging (MRI) of the loaded and nonloaded arms in 47 competitive female tennis players aged 8–17 years. Periosteal (external) cross‐sectional area (CSA), cortical area, medullary area, and the polar second moments of area (IP, mm4) were calculated at the mid and distal sites in the loaded and nonloaded arms. BMC and IPof the humerus were 11–14% greater in the loaded arm than in the nonloaded arm in prepubertal players and did not increase further in peri‐ or postpubertal players despite longer duration of loading (both, p< 0.01). The higher BMC was the result of a 7–11% greater cortical area in the prepubertal players due to greater periosteal than medullary expansion at the midhumerus and a greater periosteal expansion alone at the distal humerus. Loading late in puberty resulted in medullary contraction. Growth and the effects of loading are region and surface specific, with periosteal apposition before puberty accounting for the increase in the bone's resistance to torsion and endocortical contraction contributing late in puberty conferring little increase in resistance to torsion. Increasing the bone's resistance to torsion is achieved by modifying bone shape and mass, not necessarily bone density.

Background: Urban and rural communities differ in the incidence of several diseases including coronary heart disease and some cancers. Lower hip fracture rates among rural than urban populations have been reported but few studies have compared rural and urban fractures at sites other than the hip. Objective: To compare total and site specific fracture rates among adult residents of rural and urban communities within the same population. Design and setting: This is a population based study on osteoporosis in Australia. All fractures occurring in adult residents over a two year period were ascertained using radiological reports. The rural and urban areas are in close proximity, with the same medical, hospital, and radiological facilities permitting uniform fracture ascertainment. Main outcome measures: All fracture rates were age adjusted and sex adjusted to the Australian population according to the 1996 census of the Australian Bureau of Statistics and described as the rate per 10 000 person years. The p values refer to the adjusted rate difference. Results: The hip fracture rate (incidence per 10 000 person years) was 32% lower (39 v 57, p&lt;0.001), and the total fracture rate 15% lower (160 v 188, p=0.004) among rural than urban residents, respectively. The lower fracture rates in the rural population were also apparent for pelvic fractures. Conclusion: In the older rural population, lower fracture rates at sites typically associated with osteoporosis suggest environmental factors may have a different impact on bone health in this community. If the national rate of hip fracture could be reduced to that of the rural population, the projected increase in hip fracture number attributable to aging of the population could be prevented.

Background: Delays in bone age, the onset of puberty, and skeletal growth in gymnasts could be, in part, the reason for an interest in gymnastics, rather than being the result of vigorous exercise. We hypothesized that short stature and delayed bone age are present at the start of gymnastics, and training delays growth, producing short stature, even after retirement. Methods: Sitting height and leg length were measured in 83 active female gymnasts, 42 retired gymnasts, and 154 healthy control subjects. Results were expressed as age-specific SD scores (mean +/- SEM). Results: In the cross-sectional data, active gymnasts had delayed bone age (1.3 +/- 0.1 years), reduced height -1.32 +/- 0.08 SD, sitting height -1.24 +/- 0.09 SD, and leg length, -1.25 +/- 0.08 SD (all P < .001). However, in those training for less than 2 years, the deficit was confined to leg length (-0.8 +/- 0.2 SD). During 2 years of follow-up of 21 gymnasts, only the deficit in sitting height worsened (by 0.4 +/- 0.1 SD). In 13 gymnasts followed up in the immediate 12 months after retirement, sitting height accelerated, resulting in a lessening of the deficit in sitting height by 0.46 +/- 0.14 SD (P < .01). Adult gymnasts who had been retired for 8 years had no deficit in sitting height, leg length, or menstrual dysfunction. Conclusions: Short stature in active gymnasts is partly due to selection of individuals with reduced leg length. Reduced sitting height is likely to be acquired but is reversible with cessation of gymnastics. A history of gymnastic training does not appear to result in reduced stature or menstrual dysfunction in adulthood. (J Pediatr 2000;136:149-55)

Abstract:: There is little population-based data concerning fracture rates in Australia. We ascertained all fractures occurring during 2 years in adults aged 35 years and over residing within a defined region (population 218 000), representative of the Australian population. The major strength of this study is the comprehensive ascertainment of fractures, which was ensured by regular searches of the only two radiologic providers in the Geelong Osteoporosis Study region. Nevertheless, vertebral fractures are likely to be underestimated since our ascertainment relied on a clinical indication for a medical imaging procedure. Among those aged 35 – 55 years, the fracture rate (persons per 10 000/year) in men was about double the rate in women (65 vs 35). The fracture rate was almost 7 times higher in women over 60 years versus women less than 55 years of age. In contrast, the fracture rate in men over 60 years was only 50% higher than in men less than 55 years of age (72 vs 104). Fracture rates in women and men were highest at the hip (28 and 10 respectively), spine (21 and 7), distal forearm (Colles’) (18 and 4) and humerus (11 and 3), and were 3–4 times higher in women than men. These fractures accounted for 63% of all fractures in women and 32% in men. By contrast, the rate of lower leg and ankle fractures was less than 10 per 10 000 in both women and men and did not increase to the same extent with age. Hip fracture rates appear high, particularly among the older age strata, compared with retrospective ascertainment in other populations. In Australia, as in many other countries, there is an increasing longevity of the population. The number of women aged 90 years and over increased by 32% and the number of men of this age increased by 48% in the 5 years between the Australian national census of 1991 and 1996. Given stable fracture rates, the substantial health burden imposed by age-related fractures, particularly hip fractures, will continue to escalate in both women and men.

Abstract:: Corticosteroid therapy (CST) is associated with reduced intestinal calcium absorption, bone loss and increased fracture risk. As polymorphisms of the vitamin D receptor (VDR) gene may be associated with bone mineral density (BMD) and intestinal calcium absorption, we asked whether patients with a given VDR genotype receiving CST may be at increased or decreased risk for corticosteroid-related bone loss and osteoporosis. We measured areal BMD (g/cm2) by dual-energy X-ray absorptiometry in 193 women (50 premenopausal, 143 postmenopausal) and 70 men with rheumatoid arthritis (n= 44), obstructive airway diseases (n= 128) and other corticosteroid-treated diseases (n= 91). All patients received a cumulative dose greater than 1.8 g per year or a minimum of 5 mg daily of prednisolone or equivalent for at least 1 year. VDR alleles were typed by polymerase chain reaction assay based on the polymorphic BsmI and TaqI restriction sites. BMD in patients was expressed as a Z-score (mean � SEM) derived from age- and gender-matched controls. BMD was reduced in patients at the lumbar spine (bb, −0.52 � 0.12; Bb, −0.47 � 0.11; BB, −0.65 � 0.18 SD; p<0.01), femoral neck (bb, −0.46 � 0.10; Bb, −0.34 � 0.10; BB, −0.54 � 0.14 SD; p<0.01), Ward’s triangle (bb, −0.44 � 0.10; Bb, −0.31 � 0.10; BB, −0.45 � 0.13 SD; p<0.01), and trochanter (bb, −0.50 � 0.10; Bb, −0.30 � 0.10; BB, −0.44 � 0.14 SD; p<0.01). However, there was no significant difference in the deficit in BMD in any of the genotypes, either before or after adjusting for age, sex, body mass index, disease type, age at onset of disease, disease duration, cumulative steroid dosage, smoking status and dietary calcium intake. Similarly, there were no detectable differences between the BsmI genotypes and the rate of bone loss in 79 patients with repeated BMD measurements at an interval of 4–48 months. The data suggest that the VDR genotypes may not be a means of identifying patients at greater risk of corticosteroid-related bone loss.

Peak volumetric bone mineral density (BMD) is determined by the growth in bone size relative to the mineral accrued within its periosteal envelope. Thus, reduced peak volumetric BMD may be the result of reduced mineral accrual relative to growth in bone size. Because sex steroids and growth hormone (GH) influence bone size and mass we asked: What are the effects of gonadectomy (Gx) on bone size, bone mineral content (BMC), areal and volumetric BMD in growing male and female rats? Does GH deficiency (GH−) reduce the amount of bone in the (smaller) bone, i.e., reduce volumetric BMD? Does GH– alter the effect of Gx on bone size and mineral accrual? Gx or sham surgery was performed at 6 weeks in GH− and GH replete (GH+) Fisher 344 male and female rats. Changes in bone size, volume, BMC, areal and volumetric BMD, measured using dual X‐ray absorptiometry (DPX‐L), were expressed as percentage of controls at 8 months (mean ± SEM). All results shown were significant (p< 0.05 level) unless otherwise stated. In GH+ and GH− males, respectively, Gx was associated with: lower femur volume (24%, 25%), BMC (43%, 45%), areal BMD (21%, 14%), and volumetric BMD (30%, 28%); lower spine (L1–L3) volume (26%, 28%), BMC (26%, 30%), and areal BMD (28%, 12%), but not volumetric BMD. Following Gx, GH+ females had increased femur volume (11%), no effect on BMC, decreased areal BMD (6%) and decreased volumetric BMD (17%); GH− females had no change in femur volume, but decreased femur BMC (24%), areal BMD (10%), and volumetric BMD (25%). In GH+ and GH− females, respectively, Gx was associated with a decrease in spine (L1–L3) BMC (12%, 15%), areal BMD (16%, 15%), and volumetric BMD (10%, 16%) with no change in volume. Deficits in non‐Gx GH− relative to non‐Gx GH+ (males, females, respectively) were: femur BMC (49%, 37%), areal BMD (23%, 8%), volume (19%, 19%) and volumetric BMD (37%, 22%); spine (L1–L3) BMC (46%, 42%), areal BMD (37%, 43%), volume (10%, 15%), and volumetric BMD (40%, 33%). Testosterone and GH are growth promoting in growing male rats, producing independent effects on bone size and mass; deficiency produced smaller appendicular bones with reduced volumetric BMD because deficits in mass were greater than deficits in size. At the spine, the reduction in size and accrual were proportional, resulting in a smaller bone with normal volumetric BMD. In growing female rats, estrogen was growth limiting at appendicular sites; deficiency resulted in a GH‐dependent increase in appendicular size, relatively reduced accrual, and so, reduced volumetric BMD in a bigger bone. At the spine, accrual was reduced while growth in size was normal, thus volumetric BMD was reduced in the normal sized bone. Understanding the pathogenesis of low volumetric BMD requires the study of the differing relative growth in size and mass of the axial and appendicular skeleton in the male and female and the regulators of the growth of these traits.

Peak volumetric bone mineral density (BMD) is determined by the growth in bone size relative to the mineral accrued within its periosteal envelope. Thus, reduced peak volumetric BMD may be the result of reduced mineral accrual relative to growth in bone size. Because sex steroids and growth hormone (GH) influence bone size and mass we asked: What are the effects of gonadectomy (Gx) on bone size, bone mineral content (BMC), areal and volumetric BMD in growing male and female rats? Does GH deficiency (GH−) reduce the amount of bone in the (smaller) bone, i.e., reduce volumetric BMD? Does GH– alter the effect of Gx on bone size and mineral accrual? Gx or sham surgery was performed at 6 weeks in GH− and GH replete (GH+) Fisher 344 male and female rats. Changes in bone size, volume, BMC, areal and volumetric BMD, measured using dual X‐ray absorptiometry (DPX‐L), were expressed as percentage of controls at 8 months (mean ± SEM). All results shown were significant (p< 0.05 level) unless otherwise stated. In GH+ and GH− males, respectively, Gx was associated with: lower femur volume (24%, 25%), BMC (43%, 45%), areal BMD (21%, 14%), and volumetric BMD (30%, 28%); lower spine (L1–L3) volume (26%, 28%), BMC (26%, 30%), and areal BMD (28%, 12%), but not volumetric BMD. Following Gx, GH+ females had increased femur volume (11%), no effect on BMC, decreased areal BMD (6%) and decreased volumetric BMD (17%); GH− females had no change in femur volume, but decreased femur BMC (24%), areal BMD (10%), and volumetric BMD (25%). In GH+ and GH− females, respectively, Gx was associated with a decrease in spine (L1–L3) BMC (12%, 15%), areal BMD (16%, 15%), and volumetric BMD (10%, 16%) with no change in volume. Deficits in non‐Gx GH− relative to non‐Gx GH+ (males, females, respectively) were: femur BMC (49%, 37%), areal BMD (23%, 8%), volume (19%, 19%) and volumetric BMD (37%, 22%); spine (L1–L3) BMC (46%, 42%), areal BMD (37%, 43%), volume (10%, 15%), and volumetric BMD (40%, 33%). Testosterone and GH are growth promoting in growing male rats, producing independent effects on bone size and mass; deficiency produced smaller appendicular bones with reduced volumetric BMD because deficits in mass were greater than deficits in size. At the spine, the reduction in size and accrual were proportional, resulting in a smaller bone with normal volumetric BMD. In growing female rats, estrogen was growth limiting at appendicular sites; deficiency resulted in a GH‐dependent increase in appendicular size, relatively reduced accrual, and so, reduced volumetric BMD in a bigger bone. At the spine, accrual was reduced while growth in size was normal, thus volumetric BMD was reduced in the normal sized bone. Understanding the pathogenesis of low volumetric BMD requires the study of the differing relative growth in size and mass of the axial and appendicular skeleton in the male and female and the regulators of the growth of these traits.

The detection, prevention and treatment of disease is greatly facilitated by the availability of accurate and non-invasive techniques for measuring the amount and regional distribution of fat mass and fat-free mass. As differing degrees of hydration may influence these measurements, we used dual-energy X-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA) to detect changes in hydration following hemodialysis, and to determine whether fat mass, fat-free mass and bone density measurements were affected by these fluid changes. Ten subjects (7 men, 3 women) mean age 46.2 years (range 25–68 years), with renal failure had bone density, fat-free mass and fat mass measured by DXA, and total body water and fat-free mass measured by BIA, before and after hemodialysis. Thirty-two subjects had fat-free mass measured by DXA and BIA in an attempt to derive new equations (using fat-free mass measured by DXA as the reference standard) to improve the predictive value of BIA. The new equations were then used to derive the changes in fat-free mass following hemodialysis measured using BIA. In absolute terms, total tissue measured by DXA (r=0.99,p=0.01) and total body water measured by BIA (r=0.91,p=0.01) correlated with gravimetric weight. Following hemodialysis, fat mass and bone density measured by DXA were unaffacted by the fluid changes. The change in gravimetric weight was 1.8±0.3 kg,p=0.01 (mean±SEM). This change was measured as 1.9±0.3 kg by DXA, -0.9±1.0 kg by BIA using the published equation for fat-free mass, and 3.2±0.4 kg using the new equation for fat-free mass. The change in fat-free mass measured by DXA (r=0.75,p=0.01), and the change in total body water measured by BIA (r=0.70,p=0.02), correlated with the change in gravimetric weight. The change in fat-free mass measured by BIA did not correlate with the change in gravimetric weight. With the new equation, the change in fat-free mass measured by BIA correlated with the change in gravimetric weight (r=0.74,p=0.02). We conclude that absolute values, and changes in fluid in the range observed in this study, can be detected reliably by DXA. They are reflected in the fat-free mass measurement and do not confound measurements of fat mass and bone density. Although absolute values are reliably measured by BIA, the technique may have limited usefulness in detecting fluid changes. DXA thus provides a practical, non-invasive, precise and accurate method of measuring body composition which can be used as a ‘gold standard’ for validating other techniques.

Insulin is used to control blood glucose but may have an adverse effect on the amount and distribution of fat mass and other cardiovascular risk factors. To test this hypothesis the effect of insulin therapy on blood glucose, body composition, and lipid levels was measured during 6 months in 9 patients with newly diagnosed insulin‐dependent (Type 1) diabetes mellitus (IDDM) and 15 patients with non‐insulin dependent (Type 2) diabetes (NIDDM) and secondary failure of therapy with oral hypoglycaemic agents. Both groups received similar daily doses of insulin (∼0.6 units kg−1day−1). Glycaemic control improved during 6 months treatment in both groups, although the reduction in HbA1cwas greater in IDDM (5.2 ± 0.7 %) than in NIDDM (2.0 ± 0.4 %, p< 0.001). All parameters of the lipid profile improved in IDDM but not in NIDDM. Body weight, lean mass, and fat mass, measured by dual energy x‐ray absorptiometry, increased at 1 month in IDDM but not in NIDDM. By 6 months, body weight had increased more in IDDM than NIDDM (9.1 ± 1.2 vs 3.77 ± 0.5 kg, p< 0.01). The increase in weight was predominantly lean mass in IDDM (60.4 ± 9.3 %) and fat mass in NIDDM (59.9 ± 8.4 %). The increase in lean mass was greater in IDDM than NIDDM (5.6 ± 1.1 vs 1.4 ± 0.3 kg, p< 0.001). Fat mass increased by similar increments in IDDM and NIDDM (3.4 ± 0.8 vs 2.4 ± 0.5 kg, p= ns) and was predominantly an increase in trunk fat (IDDM: 2.3 ± 0.6 kg, NIDDM: 2.0 ± 0.4 kg, p= ns). The central/peripheral fat mass ratio prior to treatment was lower in IDDM than NIDDM (0.64 ± 0.05 vs 1.09 ± 0.09, p< 0.01) and then increased in IDDM by 0.32 ± 0.15 (p= 0.07) and in NIDDM by 0.22 ± 0.06 (p< 0.001). In conclusion, insulin therapy is associated with weight gain in both IDDM and NIDDM. In the former, weight gain reflects increases in lean mass whereas in NIDDM it reflects an increase in trunk fat mass. It remains to be determined whether this trend to central obesity partly offsets other benefits of insulin therapy in NIDDM.

Hip fractures in men account for one third of all hip fractures and have a higher mortality than in women. The public health burden will increase as the increase in the numbers of elderly men in the community increases. In addition, the age-specific incidence of hip fractures may be increasing in some, but not all, countries. Vertebral fractures may be a public health problem as recent studies suggest that the prevalence in the community is 20-30%, similar to that reported in women. Forearm fractures should probably not be regarded as a public health problem. Peak bone mass is higher in men than women because men have bigger bones. Peak bone mineral density is the same. The amount of trabecular bone lost at the spine and iliac crest during ageing is similar in men and women. Cortical bone loss is less in men because endocrotical resorption is less and periosteal formation is greater. Bone loss accelerates in elderly men because endocortical resorption and increasing cortical porosity increase the surface available for resorption. Bone fragility is less in men than women because: (a) the cross-sectional surface of the bone is larger; (b) trabecular bone loss is less as a percentage of the higher peak bone mass; (c) trabecular bone loss occurs by thinning rather than perforation; and (d) periosteal appositional growth compensates for endocortical resorption by maintaining the bending strength of bone. Reduced BMD in men with fractures may be due to reduced peak bone size and mass, and bone loss. Bone loss occurs by reduced bone formation. Whether men with fractures have increased bone fragility due to reduced periosteal appositional growth during ageing is unknown. The age-related decline in testosterone, adrenal androgens, growth hormone, and insulin-like growth factor 1 may contribute to reduced bone formation and bone loss. Men with vertebral fractures often have hypogonadism or illnesses with few clinical features that should be considered with a high index of suspicion (alcoholism, myeloma, malabsorption, primary hyperparathyroidism, haemochromatosis, Cushing's disease). Secondary hyperparathyroidism may contribute to bone loss by activating bone turnover and so increasing the number of bone remodelling units with impaired bone formation in each. There is no proven treatment for osteoporosis in men because there have been no trials using anti-fracture efficacy as an end point. Testosterone replacement should be considered in men with proven hypogonadism and vitamin D deficiency should be corrected if present. Calcium supplements and bisphosphonates are reasonable options given the lack of information.

To determine the effects of long-term daily oral alendronate sodium (ALN) on bone mass in postmenopausal women with osteoporosis, 19 centers enrolled 516 postmenopausal women aged 45–80 years with spine bone mineral density (BMD) at least 2.5 SD below the mean for young premenopausal women in a 3-year, double-blind, placebo-controlled study. Subjects were randomly allocated to one of four treatment groups: placebo; alendronate, 5 or 10 mg/day for 3 years; or alendronate, 20 mg/day for 2 years followed by 5 mg/day for the 3rd year. All patients received 500 mg/day of supplemental calcium to ensure adequate calcium intake. BMD was measured by dual-energy X-ray absorptiometry at several skeletal sites. Nonsignificant mean decreases in BMD of the spine, femoral neck, and trochanter of 0.6, 0.7, and 0.4%, respectively, occurred in the placebo group at 3 years. Relative to placebo-treated patients, spine BMD increased by 5.4%, 7.4%, and 8.4% in the 5, 10, and 20/5 mg ALN groups, respectively. Increases at the femoral neck were 3.5 %, 5.5 %, and 4.3%, and those at the trochanter were 5.1%, 7.2%, and 7.2 %, respectively. Thus, efficacy of 10 and 20/5 mg ALN was similar, whereas the 5 mg dose was less effective. BMD continned to increase over the entire 3-year study duration in the ALN-treated groups and, compared with the other dosage groups, 10 mg ALN produced the largest gains in BMD during the 3rd year. Changes in biochemical markers of bone turnover and mineral homeostasis confirmed the effect of ALN to decrease bone turnover to a new steady-state level. The safety and tolerability of ALN were comparable with those of placebo. In summary, 10 mg daily oral ALN given for 3 years significantly and progressively increases bone mass and is a generally well-tolerated treatment for osteoporosis in postmenopausal women.

The beneficial effects of corticosteroid therapy in the treatment of rheumatic diseases may be offset by the occurrence of corticosteroid-related osteoporosis. This problem may be overcome by using low-dose corticosteroids; however, the dose of corticosteroids that is both efficacious and skeletal sparing is uncertain. Therefore, the aim of this study was to determine whether low-dose prednisolone treatment results in bone loss and modifies bone turnover. Nineteen patients (12 female, seven male) suffering from polymyalgia rheumatica received 10 mg or less daily, given in reducing dosage, with a range of 2.5-10 mg and an average of 6.0 ± 0.2 mg daily (±s.E.M.). Prior to the commencement of therapy and at regular intervals during determinants of bone turnover were measured. The patients were followed for 14.4 ± 1.6 months (range 6-27). They were compared to 19 age-matched controls. Despite a mean exposure dose of 6 mg/day and disease remission, BMD decreased in the patients at the lumbar spine (2.6 ± 0.8%, P < 0.01), femoral neck (2.9 ± 1.5%, P = 0.06), Ward's triangle (5.5 ± 2.9%, P = 0.06) and the trochanter (4.3 ± 1.9%, P ± 0.05). Total body bone mass decreased by 50 ± 19 g in the first 6 months (P < 0.02), and by 39 ± 30 g in the remaining 8 months of follow-up [not significant (NS)]. In the first 6 months, BMD decreased at the lumbar spine (1.7 ± 0.9%, P = 0.06). From 6 months to the end of follow-up, BMD decreased by 8.5 ± 3.5% at Ward's triangle (P < 0.05) and by 4.8 ± 2.5% at the femoral neck (P = 0.08). The fall in BMD correlated with the cumulative prednisolone dose at trabecular-rich regions (trunk r = -0.72, P < 0.001; ribs r = -0.53, P < 0.05). Bone resorption, assessed by urinary cross-laps, was 54.7% higher than controls before treatment was started (P < 0.05) and decreased by 23.5 ± 7.1% in the first month of treatment when the mean prednisolone dose was 9.1 mg/day, range 5-10 (P < 0.0001). Serum osteocalcin was not suppressed by disease before treatment, decreased by 27.4 ± 5.1% during the first month of treatment (P < 0.001), remained suppressed while the daily dose of prednisolone was > 5 mg/day, but returned to baseline below this does. Serum parathyroid hormone was 19.3% lower in the patients than controls at baseline (NS), and increased by 46.1% (P < 0.05) but was no higher than controls at any time. Muscle strength increased by 20-60% (P < 0.05 to < 0.01). Prophylaxis should be considered in patients receiving  5 mg/day prednisolone daily as bone loss is 2- 3-fold expected rates. Earlier trabecular bone loss may predispose to spine and rib fracture; later cortical bone loss may predispose to hip fractures. Doses of prednisolone of < 5 mg daily may be skeletal sparing, but may not be efficacious.Keywords:Corticosteroid-related bone loss, Bone turnover.

The beneficial effects of corticosteroid therapy in the treatment of rheumatic diseases may be offset by the occurrence of corticosteroid-related osteoporosis. This problem may be overcome by using low-dose corticosteroids; however, the dose of corticosteroids that is both efficacious and skeletal sparing is uncertain. Therefore, the aim of this study was to determine whether low-dose prednisolone treatment results in bone loss and modifies bone turnover. Nineteen patients (12 female, seven male) suffering from polymyalgia rheumatica received 10 mg or less daily, given in reducing dosage, with a range of 2.5-10 mg and an average of 6.0 ± 0.2 mg daily (±s.E.M.). Prior to the commencement of therapy and at regular intervals during determinants of bone turnover were measured. The patients were followed for 14.4 ± 1.6 months (range 6-27). They were compared to 19 age-matched controls. Despite a mean exposure dose of 6 mg/day and disease remission, BMD decreased in the patients at the lumbar spine (2.6 ± 0.8%, P &lt; 0.01), femoral neck (2.9 ± 1.5%, P = 0.06), Ward's triangle (5.5 ± 2.9%, P = 0.06) and the trochanter (4.3 ± 1.9%, P ± 0.05). Total body bone mass decreased by 50 ± 19 g in the first 6 months (P &lt; 0.02), and by 39 ± 30 g in the remaining 8 months of follow-up [not significant (NS)]. In the first 6 months, BMD decreased at the lumbar spine (1.7 ± 0.9%, P = 0.06). From 6 months to the end of follow-up, BMD decreased by 8.5 ± 3.5% at Ward's triangle (P &lt; 0.05) and by 4.8 ± 2.5% at the femoral neck (P = 0.08). The fall in BMD correlated with the cumulative prednisolone dose at trabecular-rich regions (trunk r = -0.72, P &lt; 0.001; ribs r = -0.53, P &lt; 0.05). Bone resorption, assessed by urinary cross-laps, was 54.7% higher than controls before treatment was started (P &lt; 0.05) and decreased by 23.5 ± 7.1% in the first month of treatment when the mean prednisolone dose was 9.1 mg/day, range 5-10 (P &lt; 0.0001). Serum osteocalcin was not suppressed by disease before treatment, decreased by 27.4 ± 5.1% during the first month of treatment (P &lt; 0.001), remained suppressed while the daily dose of prednisolone was > 5 mg/day, but returned to baseline below this does. Serum parathyroid hormone was 19.3% lower in the patients than controls at baseline (NS), and increased by 46.1% (P &lt; 0.05) but was no higher than controls at any time. Muscle strength increased by 20-60% (P &lt; 0.05 to &lt; 0.01). Prophylaxis should be considered in patients receiving  5 mg/day prednisolone daily as bone loss is 2- 3-fold expected rates. Earlier trabecular bone loss may predispose to spine and rib fracture; later cortical bone loss may predispose to hip fractures. Doses of prednisolone of &lt; 5 mg daily may be skeletal sparing, but may not be efficacious.
Keywords:Corticosteroid-related bone loss, Bone turnover.

Without Abstract:

Does weight-bearing exercise offset bone loss associated with oligomenorrhea? If so, bone mineral density (BMD) will be stable at weight bearing sites but decrease at non-weight-bearing sites with increasing duration of oligomenorrhea. To test this hypothesis, BMD (g/cm2), was measured by dual-energy X-ray absorptiometry in 41 oligomenorrheic ballet dancers aged 17.7±0.2 years (mean ± SEM) and 46 age-matched controls with normal menstrual function. BMD correlated negatively with the duration of oligomenorrhea at weight-bearing and non-weight-bearing sites (femoral neck,r=-0.33,p<0.05; Ward's triangle,r=-0.29,p=0.06; trochanter, r=-0.33,p<0.05; lumbar spine,r=-0.25,p=0.1; skull,r=-0.29,p=0.06; arms,r=-0.32,p<0.05; ribs,r=-0.30,p=0.06). The slopes of the regression of BMD on duration of oligomenorrhea were greater at the proximal femur (trochanter, -0.28±0.13, femoral neck, -0.24±0.11; Ward's triangle, -0.29±0.15) than the skull (-0.15±0.08,p<0.05,p<0.1,p<0.1 respectively). The slopes at the trochanter and femoral neck were also greater than at the ribs (-0.10±0.05; bothp<0.1). In the dancers with oligomenorrhea of less than 40 months duration, BMD was higher than the age-predicted mean at weight-bearing sites (except the lumbar spine), but not at non-weight-bearing sites (femoral neck, 9.1±3.4%; Ward's triangle, 10.0±1.7%; trochanter, 9.4±4.1%, allp<0.05; lumbar spine , -2.1±2.7%, NS; skull, -2.5±2.1%, NS; ribs, -3.0±1.6% NS; arms, -3.9±1.6%;p<0.05). In the dancers with greater than 40 months oligomenorrhea, BMD was no higher than the age predicted mean, at the weight bearing sites, and was lower at non-weight bearing sites (femoral neck, 4.3±2.3%, NS; Ward's triangle, 3.5±3.2%, NS; trochanter, 2.1±2.7%, NS; lumbar spine, -3.8±2.1%, NS; arms, -7.5±0.8%,p<0.05; skull, -6.2±1.8%,p<0.01; ribs, -5.4±1.1%,p<0.0001). In conclusion, weight-bearing exercise is unlikely to offset the deleterious effects of oligomenorrhea. Bone loss appears to occur at all sites but may begin from a higher level at weight-bearing sites and may proceed more rapidly.

Osteoporosis is regarded as a disease of the elderly because fractures occur late in life. Although excessive bone loss during aging is likely to contribute to the deficit in bone density, patients with fractures do not consistently have more rapid bone loss, greater bone resorption or lower bone formation (measured using biochemical or histomorphometric markers of bone turnover). The pathogenesis of the low bone density and bone fragility that characterize osteoporosis may begin during the first two decades of life. There are differences in the hormonal regulation of regional growth and mineral accrual, differences in the age of onset, rate and duration of linear growth and mineral accrual of the axial and appendicular skeleton, of cortical and trabecular bone, and of proximal and distal limb segments. Illnesses, risk or protective factors, and disorders of hormonal deficiency or excess may affect longitudinal growth, mineral accrual, or both, depending on the timing of exposure. Quantitatively larger and qualitatively different effects on bone density may result when exposure occurs during growth rather than during adulthood. The magnitude of these deficits and their location are likely to establish the relevance of regional age-related and sex hormone dependent bone loss. Thus, any unifying hypothesis concerning the epidemiology and pathogenesis of osteoporosis must consider the relative contributions of low peak bone density and bone loss to the deficit in bone density in adulthood. A great deal of research is needed to examine the physiology of longitudinal growth and mineral accrual as the pathogenesis of osteoporosis is at least partly explained by events occurring during the first 20 years of life.

Fractures associated with severe trauma are generally excluded from estimates of the prevalence of osteoporotic fractures in the community. Because the degree of trauma is difficult to quantitate, low bone mass may contribute to fractures following severe trauma. We ascertained all fractures in a defined population and compared the bone mineral density (BMD) of women who sustained fractures in either “low” or “high” trauma events with the BMD of a random sample of women from the same population. BMD was measured by dual‐energy X‐ray absorptiometry and expressed as a standardized deviation (Z score) adjusted for age. The BMD Z scores (mean ± SEM) were reduced in both the low and high trauma groups, respectively: spine‐posterior‐anterior (−0.50 ± 0.05 and −0.21 ± 0.08), spine‐lateral (−0.28 ± 0.06 and −0.19 ± 0.10), femoral neck (−0.42 ± 0.04 and −0.26 ± 0.09), Ward's triangle (−0.44 ± 0.04 and −0.28 ± 0.08), trochanter (−0.44 ± 0.05 and −0.32 ± 0.08), total body (−0.46 ± 0.06 and −0.32 ± 0.08), ultradistal radius (−0.47 ± 0.05 and −0.42 ± 0.07), and midradius (−0.52 ± 0.06 and −0.33 ± 0.09). Except at the PA spine, the deficits were no smaller in the high trauma group. Compared with the population, the age‐adjusted odds ratio for osteoporosis (t‐score < −2.5) at one or more scanning sites was 3.1 (95% confidence interval 1.9, 5.0) in the high trauma group and 2.7 (1.9, 3.8) in the low trauma group. The data suggest that the exclusion of high trauma fractures in women over 50 years of age may result in underestimation of the contribution of osteoporosis to fractures in the community. Bone density measurement of women over 50 years of age who sustain fractures may be warranted irrespective of the classification of trauma.

Cross‐sectional studies of elite athletes suggest that growth is an opportune time for exercise to increase areal bone mineral density (BMD). However, as the exercise undertaken by athletes is beyond the reach of most individuals, these studies provide little basis for making recommendations regarding the role of exercise in musculoskeletal health in the community. To determine whether moderate exercise increases bone mass, size, areal, and volumetric BMD, two socioeconomically equivalent schools were randomly allocated to be the source of an exercise group or controls. Twenty boys (mean age 10.4 years, range 8.4–11.8) allocated to 8 months of 30‐minute sessions of weight‐bearing physical education lessons three times weekly were compared with 20 controls matched for age, standing and sitting height, weight, and baseline areal BMD. Areal BMD, measured using dual‐energy X‐ray absorptiometry, increased in both groups at all sites, except at the head and arms. The increase in areal BMD in the exercise group was twice that in controls; lumbar spine (0.61 ± 0.11 vs. 0.26 ± 0.09%/month), legs (0.76 ± 0.07 vs. 0.34 ± 0.08%/month), and total body (0.32 ± 0.04 vs. 0.17 ± 0.06%/month) (all p< 0.05). In the exercise group, femoral midshaft cortical thickness increased by 0.97 ± 0.32%/month due to a 0.93 ± 0.33%/month decrease in endocortical (medullary) diameter (both p< 0.05). There was no periosteal expansion so that volumetric BMD increased by 1.14 ± 0.33%/month, (p< 0.05). Cortical thickness and volumetric BMD did not change in controls. Femoral midshaft section modulus increased by 2.34 ± 2.35 cm3in the exercise group, and 3.04 ± 1.14 cm3in controls (p< 0.05). The growing skeleton is sensitive to exercise. Moderate and readily accessible weight‐bearing exercise undertaken before puberty may increase femoral volumetric BMD by increasing cortical thickness. Although endocortical apposition may be a less effective means of increasing bone strength than periosteal apposition, both mechanisms will result in higher cortical thickness that is likely to offset bone fragility conferred by menopause‐related and age‐related endocortical bone resorption.

Fractures associated with severe trauma are generally excluded from estimates of the prevalence of osteoporotic fractures in the community. Because the degree of trauma is difficult to quantitate, low bone mass may contribute to fractures following severe trauma. We ascertained all fractures in a defined population and compared the bone mineral density (BMD) of women who sustained fractures in either “low” or “high” trauma events with the BMD of a random sample of women from the same population. BMD was measured by dual‐energy X‐ray absorptiometry and expressed as a standardized deviation (Z score) adjusted for age. The BMD Z scores (mean ± SEM) were reduced in both the low and high trauma groups, respectively: spine‐posterior‐anterior (−0.50 ± 0.05 and −0.21 ± 0.08), spine‐lateral (−0.28 ± 0.06 and −0.19 ± 0.10), femoral neck (−0.42 ± 0.04 and −0.26 ± 0.09), Ward's triangle (−0.44 ± 0.04 and −0.28 ± 0.08), trochanter (−0.44 ± 0.05 and −0.32 ± 0.08), total body (−0.46 ± 0.06 and −0.32 ± 0.08), ultradistal radius (−0.47 ± 0.05 and −0.42 ± 0.07), and midradius (−0.52 ± 0.06 and −0.33 ± 0.09). Except at the PA spine, the deficits were no smaller in the high trauma group. Compared with the population, the age‐adjusted odds ratio for osteoporosis (t‐score < −2.5) at one or more scanning sites was 3.1 (95% confidence interval 1.9, 5.0) in the high trauma group and 2.7 (1.9, 3.8) in the low trauma group. The data suggest that the exclusion of high trauma fractures in women over 50 years of age may result in underestimation of the contribution of osteoporosis to fractures in the community. Bone density measurement of women over 50 years of age who sustain fractures may be warranted irrespective of the classification of trauma.

Cross‐sectional studies of elite athletes suggest that growth is an opportune time for exercise to increase areal bone mineral density (BMD). However, as the exercise undertaken by athletes is beyond the reach of most individuals, these studies provide little basis for making recommendations regarding the role of exercise in musculoskeletal health in the community. To determine whether moderate exercise increases bone mass, size, areal, and volumetric BMD, two socioeconomically equivalent schools were randomly allocated to be the source of an exercise group or controls. Twenty boys (mean age 10.4 years, range 8.4–11.8) allocated to 8 months of 30‐minute sessions of weight‐bearing physical education lessons three times weekly were compared with 20 controls matched for age, standing and sitting height, weight, and baseline areal BMD. Areal BMD, measured using dual‐energy X‐ray absorptiometry, increased in both groups at all sites, except at the head and arms. The increase in areal BMD in the exercise group was twice that in controls; lumbar spine (0.61 ± 0.11 vs. 0.26 ± 0.09%/month), legs (0.76 ± 0.07 vs. 0.34 ± 0.08%/month), and total body (0.32 ± 0.04 vs. 0.17 ± 0.06%/month) (all p< 0.05). In the exercise group, femoral midshaft cortical thickness increased by 0.97 ± 0.32%/month due to a 0.93 ± 0.33%/month decrease in endocortical (medullary) diameter (both p< 0.05). There was no periosteal expansion so that volumetric BMD increased by 1.14 ± 0.33%/month, (p< 0.05). Cortical thickness and volumetric BMD did not change in controls. Femoral midshaft section modulus increased by 2.34 ± 2.35 cm3in the exercise group, and 3.04 ± 1.14 cm3in controls (p< 0.05). The growing skeleton is sensitive to exercise. Moderate and readily accessible weight‐bearing exercise undertaken before puberty may increase femoral volumetric BMD by increasing cortical thickness. Although endocortical apposition may be a less effective means of increasing bone strength than periosteal apposition, both mechanisms will result in higher cortical thickness that is likely to offset bone fragility conferred by menopause‐related and age‐related endocortical bone resorption.

Exercise during growth may contribute to the prevention of osteoporosis by increasing peak bone mineral density (BMD). However, exercise during puberty may be associated with primary amenorrhea and low peak BMD, while exercise after puberty may be associated with secondary amenorrhea and bone loss. As growth before puberty is relatively sex hormone independent, are the prepubertal years the time during which exercise results in higher BMD? Are any benefits retained in adulthood? We measured areal BMD (g/cm2) by dual‐energy X‐ray absorptiometry in 45 active prepubertal female gymnasts aged 10.4 ± 0.3 years (mean ± SEM), 36 retired female gymnasts aged 25.0 ± 0.9 years, and 50 controls. The results were expressed as a standardized deviation (SD) or Z score adjusted for bone age in prepubertal gymnasts and chronological age in retired gymnasts. In the cross‐sectional analyses, areal BMD in the active prepubertal gymnasts was 0.7–1.9 SD higher at the weight‐bearing sites than the predicted mean in controls (p< 0.01). The Z scores increased as the duration of training increased (r= 0.32–0.48, pranging between <0.04 and <0.002). During 12 months, the increase in areal BMD (g/cm2/year) of the total body, spine, and legs in the active prepubertal gymnasts was 30–85% greater than in prepubertal controls (all p< 0.05). In the retired gymnasts, the areal BMD was 0.5–1.5 SD higher than the predicted mean in controls at all sites, except the skull (pranging between <0.06 and <0.0001). There was no diminution across the 20 years since retirement (mean 8 ± 1 years), despite the lower frequency and intensity of exercise. The prepubertal years are likely to be an opportune time for exercise to increase bone density. As residual benefits are maintained into adulthood, exercise before puberty may reduce fracture risk after menopause.

Understanding of the genetic and environmental factors contributing to the differences in fracture rates between young and old, between women and men, and between races is limited. The reasons for this may partly relate to the lack of a detailed understanding of the structural basis of bone fragility. This information, although difficult to obtain because of the invasiveness of bone biopsy, will be required if advances are to occur. aBMD cannot be relied upon as an endpoint in the study of the pathophysiology of osteoporosis. Advances will require the description of the age-, gender and race-specific means and variances in trabecular number, thickness, spacing and orientation, cortical thickness, and bone size and shape in women and men of different racial groups. Subsequent comparison of the structures in young versus old, female versus male, and in racial groups may reveal the structural differences from which inferences may be made concerning the differences in fracture rates between these groups. By defining the structural basis for bone fragility, the genetic andmodifiableenvironmental determinants of these structures may then be identified, providing hypotheses to be tested in randomized trials aimed at reducing the incidence of fractures in these groups.

Exercise during growth may contribute to the prevention of osteoporosis by increasing peak bone mineral density (BMD). However, exercise during puberty may be associated with primary amenorrhea and low peak BMD, while exercise after puberty may be associated with secondary amenorrhea and bone loss. As growth before puberty is relatively sex hormone independent, are the prepubertal years the time during which exercise results in higher BMD? Are any benefits retained in adulthood? We measured areal BMD (g/cm2) by dual‐energy X‐ray absorptiometry in 45 active prepubertal female gymnasts aged 10.4 ± 0.3 years (mean ± SEM), 36 retired female gymnasts aged 25.0 ± 0.9 years, and 50 controls. The results were expressed as a standardized deviation (SD) or Z score adjusted for bone age in prepubertal gymnasts and chronological age in retired gymnasts. In the cross‐sectional analyses, areal BMD in the active prepubertal gymnasts was 0.7–1.9 SD higher at the weight‐bearing sites than the predicted mean in controls (p< 0.01). The Z scores increased as the duration of training increased (r= 0.32–0.48, pranging between <0.04 and <0.002). During 12 months, the increase in areal BMD (g/cm2/year) of the total body, spine, and legs in the active prepubertal gymnasts was 30–85% greater than in prepubertal controls (all p< 0.05). In the retired gymnasts, the areal BMD was 0.5–1.5 SD higher than the predicted mean in controls at all sites, except the skull (pranging between <0.06 and <0.0001). There was no diminution across the 20 years since retirement (mean 8 ± 1 years), despite the lower frequency and intensity of exercise. The prepubertal years are likely to be an opportune time for exercise to increase bone density. As residual benefits are maintained into adulthood, exercise before puberty may reduce fracture risk after menopause.

ObjectiveTo assess the antifracture efficacy and safety of a nutritional intervention in institutionalised older adults replete in vitamin D but with mean intakes of 600 mg/day calcium and <1 g/kg body weight protein/day.DesignTwo year cluster randomised controlled trial.Setting60 accredited residential aged care facilities in Australia housing predominantly ambulant residents.Participants7195 permanent residents (4920 (68%) female; mean age 86.0 (SD 8.2) years).InterventionFacilities were stratified by location and organisation, with 30 facilities randomised to provide residents with additional milk, yoghurt, and cheese that contained 562 (166) mg/day calcium and 12 (6) g/day protein achieving a total intake of 1142 (353) mg calcium/day and 69 (15) g/day protein (1.1 g/kg body weight). The 30 control facilities maintained their usual menus, with residents consuming 700 (247) mg/day calcium and 58 (14) g/day protein (0.9 g/kg body weight).Main outcome measuresGroup differences in incidence of fractures, falls, and all cause mortality.ResultsData from 27 intervention facilities and 29 control facilities were analysed. A total of 324 fractures (135 hip fractures), 4302 falls, and 1974 deaths were observed. The intervention was associated with risk reductions of 33% for all fractures (121 v203; hazard ratio 0.67, 95% confidence interval 0.48 to 0.93; P=0.02), 46% for hip fractures (42 v93; 0.54, 0.35 to 0.83; P=0.005), and 11% for falls (1879 v2423; 0.89, 0.78 to 0.98; P=0.04). The risk reduction for hip fractures and falls achieved significance at five months (P=0.02) and three months (P=0.004), respectively. Mortality was unchanged (900 v1074; hazard ratio 1.01, 0.43 to 3.08).ConclusionsImproving calcium and protein intakes by using dairy foods is a readily accessible intervention that reduces the risk of falls and fractures commonly occurring in aged care residents.Trial registrationAustralian New Zealand Clinical Trials Registry ACTRN12613000228785.

Strontium ranelate is an orally active drug that may permit ongoing production of bone while at the same time reducing bone resorption. New vertebral fractures reportedly are less frequent in postmenopausal women who receive this agent. The Treatment of Peripheral Osteoporosis Study (TROPOS) is a randomized, double-blind, placebo-controlled trial designed to show whether strontium ranelate prevents nonvertebral fractures in European and Australian postmenopausal women who had a bone mineral density (BMD) equivalent to a T-score less than −2.5. Participants were 74 years or older, or 70 to 74 years if an additional fracture risk factor was present. Either strontium ranelate in a daily dose of 2 g or placebo was given to 5091 postmenopausal women with osteoporosis. Major statistical analysis was undertaken over 3 years of treatment. The intention-to-treat population totaled 4932 patients.

Abstract:: Hip axis length (HAL) has been reported as an independent risk factor for hip fracture. Later puberty may increase bone size because of delayed epiphyseal fusion. We sought to identify associations between bone size at the proximal femur with age at menarche and other indices of growth such as stature. Femoral neck dimensions were measured from dual-energy X-ray absorptiometry scans of the proximal femur in a random sample of 203 premenopausal Caucasian women (age 20–30 years). There were no associations between age at menarche and HAL, femoral axis length (FAL) or femoral neck width (FNW). Age at menarche was associated with height (r= 0.2, p= 0.02). Variations in HAL, FAL and FNW do not appear to be related to age at menarche.