The Cost of Osteoporosis, Osteopenia, and Associated Fractures in Australia in 2017.

Osteoporosis and osteopenia are increasingly prevalent conditions among older adults. Not only do the fractures associated with poor bone health have significant health consequences for the individual, but also their economic impact is placing increasing financial burden on governments and society. This study aimed to determine the direct economic cost of osteoporosis, osteopenia, and fractures among Australians aged 50 years and older in 2017. This study uses previous Australian data on the incidence and prevalence of osteoporosis and osteopenia together with recent Australian data on health service utilization after fracture to provide an estimate of the economic burden of osteoporosis. A bottom-up costing approach was used to determine the average direct health care and non-health care total costs of a fracture, as well as the average community health service costs of managing individuals with osteoporosis or osteopenia. The total direct cost of osteoporosis in Australia in 2017 was estimated to be $3.44 billion (AUD 2017, USD 2.77 billion). Treatment of fractures accounted for 68% of total direct costs, and non-fracture management of osteoporosis accounted for 32%. Hip fractures accounted for the highest proportion (43%) of the total direct cost of fractures, although fractures at "other" sites accounted for 38.5%. Fractures among individuals aged 70 years and older accounted for 74% of the direct costs (55% and 19% in women and men, respectively). Fracture costs in those with osteopenia accounted for 50% of direct fracture treatment costs. This up-to-date cost analysis estimated that costs in 2017 were three times higher than in 2007. These estimates will aid clinicians, policy makers, researchers, and health care organizations to acknowledge the economic importance of reducing osteoporosis-related fractures and associated costs. This provides a strong public health case to promote bone health that will assist in reducing future fracture-related costs. © 2018 American Society for Bone and Mineral Research.

Immunological and nutritional factors in elderly people in low-level care and their association with mortality.

BACKGROUND: This study examines associations between markers of nutritional status and lymphocyte subsets and seeks to determine if lymphocyte profile is predictive of survival in elderly Australians residing in aged care facilities. Aged yet still ambulatory subjects (n = 88, 73% female) living in low-level care and requiring minimal assistance were studied for 143 weeks. At baseline when participants were aged (mean ± SD) 86.0 ± 5.9 years, dietary intake was determined by 3-day weighed food record, body composition was assessed by dual energy X-ray absorptiometry (DXA) and a venous blood sample was taken. RESULTS: At baseline assessment, study participants were consuming nutrient-poor diets and most had symptoms of chronic disease. Although overweight, 40% exhibited sarcopenia. Markers of nutritional status did not relate closely to immune cell numbers (absolute or relative), which on average were within the normal range. Men had lower numbers of CD3(+)CD4(+) cells (CD4(+) T cells), a higher proportion of CD3(-) CD16(±) CD56(±) (natural killer (NK) cells) and a higher ratio of NK: CD4(+) T cells than women (all P < 0.05). The main age-related changes evident were decreased T cells, particularly low CD4(+) T cell counts, and increased numbers of CD19(+) (B-cell) and NK cells. During the 143 week duration of follow-up, about one quarter of the study participants died, with death more likely in men than women (P < 0.01). Poor survival was predicted by the presence of decreased numbers of CD4(+) T cells (hazard ratio (HR) 0.919, P < 0.01) and expanded numbers of NK cells (HR 1.085, P < 0.05) in the blood, and therefore the presence of a high NK: CD4(+) T cell ratio (HR 30.521, P < 0.01). CONCLUSIONS: THE NK: CD4(+) T cell ratio may potentially have clinical utility for predicting longevity in elderly populations. Further studies are needed in other elderly populations to confirm this finding.

Teriparatide improves bone quality and healing of atypical femoral fractures associated with bisphosphonate therapy.

Bone remodelling suppressants like the bisphosphonates reduce bone loss and slow progression of structural decay. As remodelling removes damaged bone, when remodelling suppression is protracted, bone quality may be compromised predisposing to microdamage accumulation and atypical femoral fractures. The aim of this study was to determine whether teriparatide therapy assists in fracture healing and improves bone quality in patients with bisphosphonate associated atypical femoral fractures. A prospective study was conducted involving 14 consecutive patients presenting during 2 years with atypical femoral fracture. All patients were offered teriparatide therapy unless contraindicated. Age and sex matched control subjects without fragility fractures or anti-resorptive treatment were recruited. High resolution peripheral micro-computed tomography (HRpQCT) scans of the distal radius and distal tibia were analysed for their cortical bone tissue mineralisation density using new software (StrAx1.0, StrAxCorp, Australia) at baseline and 6 months after teriparatide. Administration of 20 µg of teriparatide subcutaneously daily for 6 months to 5 of the 14 patients was associated with 2-3 fold increase in bone remodelling markers (p=0.01) and fracture healing. At the distal radius, the proportion of less densely mineralised bone increased by 29.5% (p=0.01), and the proportion of older, more densely mineralised bone decreased by 16.2% (p=0.03). Similar observations were made at the distal tibia. Of the nine patients managed conservatively or surgically, seven had poor fracture healing with ongoing pain, one sustained a contralateral atypical fracture and one had fracture union after 1 year. Teriparatide may assist in healing of atypical fractures and restoration of bone quality.

Stepping towards prevention of bone loss after stroke: a systematic review of the skeletal effects of physical activity after stroke.

Bone loss after stroke is pronounced, and contributes to increased fracture risk. People who fracture after stroke experience reduced mobility and increased mortality. Physical activity can maintain or improve bone mineral density and structure in healthy older adults, likely reducing fracture risk. The purpose of this systematic review was to investigate the skeletal effects of physical activity in adults affected by stroke. A search of electronic databases was undertaken. Selection criteria of trials were • prospective and controlled • physical activity-based intervention • participants with history of stroke, and • bone-related outcome measures. Effect sizes were calculated for outcomes of paretic and nonparetic limbs. Three of 349 identified records met the inclusion criteria. Small effect sizes were found in favor of physical activity in adults with chronic stroke (n=95, 40% female, average age 63·8 years, more than one-year poststroke). Patients in intervention groups had significantly higher changes in femoral neck bone mineral density, tibial cortical thickness and trabecular bone mineral content of the paretic limb, compared with controls (P<0·05). It is not known whether these benefits reduced fracture risk. There are limited studies investigating the skeletal effect of physical activity for adults poststroke. Given the increased risk of, and poor outcomes following a fracture after stroke, randomized trials are warranted to investigate the benefits of physical activity on bone, after stroke. Interventions are likely to be beneficial if implemented soon after stroke, when bone loss appears to be rapid and pronounced.

Poor physical function in elderly women in low-level aged care is related to muscle strength rather than to measures of sarcopenia.

PURPOSE: To determine the prevalence of sarcopenia and investigate relationships among body composition, muscle strength, and physical function in elderly women in low-level aged care. SUBJECTS AND METHODS: Sixty-three ambulatory women (mean age 86 years) participated in this cross-sectional study where body composition was determined by dual energy X-ray absorptiometry (DXA); ankle, knee, and hip strength by the Nicholas Manual Muscle Tester; and physical function by 'timed up and go' (TUG) and walking speed (WS) over 6 meters. Body composition data from a female reference group (n = 62, mean age 29 years) provided cut-off values for defining sarcopenia. RESULTS: Elderly women had higher body mass index (P < 0.001), lower lean mass (P < 0.001), and higher fat mass (P < 0.01) than the young reference group. Only a small proportion (3.2%) had absolute sarcopenia (defined by appendicular skeletal muscle mass/height squared) whereas 37% had relative sarcopenia class II (defined by percentage skeletal muscle mass). Scores for TUG and WS indicated relatively poor physical function, yet these measures were not associated with muscle mass or indices of sarcopenia. In multivariate analysis, only hip abductor strength predicted both TUG and WS (both P = 0.01). CONCLUSION: Hip strength is a more important indicator of physical functioning than lean mass. Measurement of hip strength may therefore be a useful screening tool to detect those at risk of functional decline and requirement for additional care. Further longitudinal studies with a range of other strength measures are warranted.

Trabecular bone of growth plate origin influences both trabecular and cortical morphology in adulthood.

Skeletal fragility is common at metaphyseal regions of long bones. The cortices of this region are derived by coalescence of trabeculae around the periphery of the growth plate, not by periosteal apposition, as occurs in the diaphyses. We therefore hypothesized that trabecular bone in childhood predicted both cortical and trabecular morphology in adulthood. To test this hypothesis, we measured distal radial and tibial structure using high-resolution peripheral quantitative computed tomography in 61 daughter-mother pairs, mean age 12.5 years (range 7 to 19 years) and 44.1 years (range 32 to 50 years), respectively. The daughters' trabecular bone volume (BV/TV), thickness, number, and separation predicted the corresponding traits in their mothers. Their trabecular BV/TV also predicted their mothers' cortical thickness (r = 0.32, p = .02). By contrast, the daughters' cortical thickness did not predict their mothers' cortical thickness. The daughters had higher trabecular BV/TV than their mothers (mean ± SD, radius 0.134 ± 0.024 versus 0.124 ± 0.033, p = .03; tibia 0.145 ± 0.021 versus 0.135 ± 0.032, p < .01) owing to greater trabecular number, not thickness, and less trabecular separation. Abnormalities in the development of metaphyseal trabecular bone are likely to influence fragility in both trabecular and cortical bone of this region in adulthood.

Weight loss in elderly women in low-level care and its association with transfer to high-level care and mortality.

BACKGROUND: The purpose of this study was to determine whether unintentional weight loss in older women predicts an imminent transition out of low-level care (either to higher-level care or by mortality). METHODS: Fifty-three Australian women, ambulatory while living in low-level care and requiring minimal assistance, were studied. At baseline, when the women were aged (mean ± standard deviation) 86.2 ± 5.3 years, body composition was assessed by dual energy X-ray absorptiometry, dietary intake was determined by a three-day weighed food record, a venous blood sample was taken, and both muscle strength and physical functioning were measured. The women were then followed up for 143 weeks to record the composite outcome of transfer to high-level care or mortality. RESULTS: During follow-up, unintended loss of body weight occurred in 60% of the women, with a mean weight loss of -4.6 ± 3.6 kg. Seven women (13.2%) died, and seven needed transfer to high-level care. At baseline, those who subsequently lost weight had a higher body mass index (P < 0.01) because they were shorter (P < 0.05) but not heavier than the other women. Analysis of their dietary pattern revealed a lower dietary energy (P < 0.05) and protein intake (P < 0.01). The women who lost weight also had lower hip abductor strength (P < 0.01), took longer to stand and walk (P < 0.05), and showed a slower walking speed (P < 0.01). Their plasma C-reactive protein was higher (P < 0.05) and their serum albumin was lower (P < 0.01) than women who did not lose weight. Nonintentional weight loss was a significant predictor of death or transfer to high care (hazards ratio 0.095, P = 0.02). CONCLUSION: Weight loss in older women predicts adverse outcomes, so should be closely monitored.

Intracortical remodelling and porosity in the distal radius and post-mortem femurs of women: a cross-sectional study.

BACKGROUND: Osteoporosis research has focused on vertebral fractures and trabecular bone loss. However, non-vertebral fractures at predominantly cortical sites account for 80% of all fractures and most fracture-related morbidity and mortality in old age. We aimed to re-examine cortical bone as a source of bone loss in the appendicular skeleton. METHODS: In this cross-sectional study, we used high-resolution peripheral CT to quantify and compare cortical and trabecular bone loss from the distal radius of adult women, and measured porosity using scanning electron microscopy. Exclusion criteria were diseases or prescribed drugs affecting bone metabolism. We also measured bone mineral density of post-mortem hip specimens from female cadavers using densitometry. Age-related differences in total, cortical, and trabecular bone mass, trabecular bone of cortical origin, and cortical and trabecular densities were calculated. FINDINGS: We investigated 122 white women with a mean age of 62.8 (range 27-98) years. Between ages 50 and 80 years (n=89), 72.1 mg (95% CI 67.7-76.4) hydroxyapatite (68%) of 106.5 mg hydroxyapatite of bone lost at the distal radius was cortical and 34.3 mg (30.5-37.8) hydroxyapatite (32%) was trabecular; 17.1 mg (11.7-22.5) hydroxyapatite (16%) of total bone loss occurred between ages 50 and 64 years (n=34) and 89.4 mg (83.7-101.1) hydroxyapatite (84%) after age 65 years (n=55). Remodelling within cortex adjacent to the marrow accounted for 49.9 mg (45.4-53.7) hydroxyapatite (47%) of bone loss. Between ages 50-64 years (n=34) and 80 years and older (n=33), cortical density decreased by 127.8 mg (93.1-162.1) hydroxyapatite per cm(3) (15%, p<0.0001) before porosity trabecularising the cortex was included, but 374.3 mg (318.2-429.5) hydroxyapatite per cm(3) (43%, p<0.0001) after; trabecular density decreased by 18.2 mg (-1.4 to 38.2) hydroxyapatite per cm(3) (14%, p=0.06) before cortical remnants were excluded, but 68.7 mg (37.7-90.4) hydroxyapatite per cm(3) (52%, p<0.0001) after. INTERPRETATION: Accurate assessment of bone structure, especially porosity producing cortical remnants, could improve identification of individuals at high and low risk of fracture and therefore assist targeting of treatment. FUNDING: Australia National Health and Medical Research Council.

Rapid growth produces transient cortical weakness: a risk factor for metaphyseal fractures during puberty.

Fractures of the distal radius in children have a similar incidence to that found in postmenopausal women but occur more commonly in boys than in girls. Fractures of the distal tibia are uncommon in children and show no sex specificity. About 90% of lengthening of the radius but only 30% of lengthening of the tibia during puberty occur at the distal growth plate. We speculated that more rapid modeling at the distal radial metaphysis results in a greater dissociation between growth and mineral accrual than observed at the distal tibia. We measured the macro- and microarchitecture of the distal radial and tibial metaphysis using high-resolution peripheral quantitative computed tomography in a cross-sectional study of 69 healthy boys and 60 healthy girls aged from 5 to 18 years. Bone diameters were larger but total volumetric bone mineral density (vBMD) was lower at the distal radius (not at the distal tibia) by 20% in boys and by 15% in girls at Tanner stage III than in children of the same sex at Tanner stage I (both p < .05). In boys at Tanner stage III, total vBMD was lower because the larger radial total cross-sectional area (CSA) had a thinner cortex with lower vBMD than in boys at Tanner stage I. In girls at Tanner stage III, the larger total radial CSA was not associated with a difference in cortical thickness or cortical vBMD relative to girls in Tanner stage I. Cortical thickness and density at both sites in both sexes after Tanner stage III were greater than in younger children. Trabecular bone volume fraction (BV/TV) was higher in boys than in girls at both sites and more so after puberty because trabeculae were thicker in more mature boys but not in girls. There was no sex- or age-related differences in trabecular number at either site. We infer that longitudinal growth outpaces mineral accrual in both sexes at the distal radius, where bone grows rapidly. The dissociation produces transitory low cortical thickness and vBMD in boys but not in girls. These structural features in part may account for the site and sex specificity of metaphyseal fractures during growth.

Differences in macro- and microarchitecture of the appendicular skeleton in young Chinese and white women.

To identify the racial differences in macro- and microstructure of the distal radius and tibia that may account for the lower fracture rates in Asians than whites, we studied 61 healthy premenopausal Chinese and 111 white women 18-45 yr of age using high-resolution pQCT (HR-pQCT). The Chinese were shorter and leaner. Distal radius total cross-sectional area (CSA) was 14.3% smaller in Chinese because of an 18.0% smaller trabecular area (p < 0.001). Cortical thickness was 8.8% greater in the Chinese, but cortical area was no different. Total volumetric BMD (vBMD) was 10.3% higher in the Chinese because of the 8.8% higher cortical thickness and 2.8% greater cortical density (all p < 0.01). Trabecular vBMD and bone volume/tissue volume (BV/TV) did not differ by race because trabeculae were 7.0% fewer but 10.8% thicker in Chinese than whites (both p < 0.01). Similar results were found at the distal tibia. Lower fracture risk in Chinese women may be partly caused by thicker cortices and trabeculae in a smaller bone-more bone within the bone than in whites.

The age of puberty determines sexual dimorphism in bone structure: a male/female co-twin control study.

BACKGROUND: Taller stature and larger bone size in males are attributed to more rapid growth than in females. However, comparing sexes of the same age mismatches by pubertal stage, so males will be less mature than females. Comparing sexes of the same pubertal stage mismatches by age, so males will be older than females. OBJECTIVE: We hypothesized that sex differences in stature and bone structure are the result of sex differences in the duration but not the rate of prepubertal and pubertal growth. METHODS: We measured bone dimensions in 90 male/female co-twin pairs aged 7-18 yr using anthropometry and dual x-ray absorptiometry. Forty-two pairs had follow-up assessments. Within-pair differences were expressed as a percentage of the pair mean. RESULTS: Thirty percent of the 1-1.5 sd sex difference in bone widths and midfemur bending strength observed in 11 postpubertal pairs was present in 43 prepubertal pairs. In prepubertal pairs, annual growth in leg length was about 1.5 times truncal growth, but neither rate differed by sex. During puberty, truncal growth in both sexes was higher than before puberty but did not differ by sex. The longer period of pre- and intrapubertal growth in males produced most of the sex difference in bone morphology observed in postpubertal twins. CONCLUSION: Sex differences in bone morphology are the result of the later onset of puberty in males, not more rapid growth. Differences in bone widths are partly established before puberty.

Exercise and calcium combined results in a greater osteogenic effect than either factor alone: a blinded randomized placebo-controlled trial in boys.

UNLABELLED: We examined the combined effects of exercise and calcium on BMC accrual in pre- and early-pubertal boys. Exercise and calcium together resulted in a 2% greater increase in femur BMC than either factor alone and a 3% greater increase in BMC at the tibia-fibula compared with the placebo group. Increasing dietary calcium seems to be important for optimizing the osteogenic effects of exercise. INTRODUCTION: Understanding the relationship between exercise and calcium during growth is important given that the greatest benefits derived from these factors are achieved during the first two decades of life. We conducted a blinded randomized-controlled exercise-calcium intervention in pre- and early-pubertal boys to test the following hypotheses. (1) At the loaded sites (femur and tibia-fibula), exercise and calcium will produce greater skeletal benefits than either exercise or calcium alone. (2) At nonloaded sites (humerus and radius-ulna), there will be an effect of calcium supplementation. MATERIALS AND METHODS: Eighty-eight pre- and early-pubertal boys were randomly assigned to one of four study groups: moderate impact exercise with or without calcium (Ca) (Ex+Ca and Ex+placebo, respectively) or low impact exercise with or without Ca (No-Ex+Ca and No-Ex+Placebo, respectively). The intervention involved 20 minutes of either moderate- or low-impact exercise performed three times a week and/or the addition of Ca-fortified foods using milk minerals (392+/-29 mg/day) or nonfortified foods over 8.5 months. Analysis of covariance was used to determine the main and combined effects of exercise and calcium on BMC after adjusting for baseline BMC. RESULTS: At baseline, no differences were reported between the groups for height, weight, BMC, or bone length. The increase in femur BMC in the Ex+Ca group was approximately 2% greater than the increase in the Ex+placebo, No-Ex+Ca, or No-Ex+Placebo groups (all p<0.03). At the tibia-fibula, the increase in BMC in the Ex+Ca group was approximately 3% greater than the No-Ex+placebo group (p<0.02) and 2% greater than the Ex+Placebo and the No-Ex+Ca groups (not significant). No effect of any group was detected at the humerus, ulna-radius, or lumbar spine for BMC, height, bone area, or volume. CONCLUSIONS: In this group of normally active boys with adequate calcium intakes, additional exercise and calcium supplementation resulted in a 2-3% greater increase in BMC than controls at the loaded sites. These findings strengthen the evidence base for public health campaigns to address both exercise and dietary changes in children for optimizing the attainment of peak BMC.

Depression in anorexia nervosa: a risk factor for osteoporosis.

CONTEXT: Both anorexia nervosa (AN) and depression are associated with osteoporosis. We hypothesized that adolescent girls with AN and depression will have lower bone mineral density (BMD) than anorexic girls without depression. OBJECTIVE: The objective of this study was to investigate whether depression is an independent risk factor for osteoporosis in anorexic adolescent girls. DESIGN: This study was cross-sectional. SETTING: This study was conducted at the University Children's Hospital (Bialystok, Poland) from October 2002 through September 2003. PARTICIPANTS: Forty-five Caucasian anorexic girls aged 13-23 yr, matched by age, Tanner stage, weight, height, calcium intake, and duration of AN, were studied, including 14 with comorbid depression (based on Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale) and 31 anorexic girls without depression. MAIN OUTCOME MEASURES: Total body and lumbar spine (LS) BMD, fat mass, and lean mass assessed using dual-energy x-ray absorptiometry were compared between AN girls with and without depression. RESULTS: BMD was reduced in both groups, relative to reference data, but girls with AN and depression had lower BMD than those with AN alone (LS Z-scores, -2.6 +/- 0.3 vs. -1.7 +/- 0.3; P = 0.02) (mean +/- sem). Quantitative assessment of depression correlated independently with total body BMD (r = -0.4; P < 0.05) and LS BMD (r = -0.6; P < 0.001). CONCLUSION: Anorexic girls with depression are at higher risk of osteoporosis than those without depression. The mechanisms responsible for decreased BMD in depression are not known. Independent treatment of the depressive disorder in AN may partly alleviate the bone fragility.

Diet and exercise during growth have site-specific skeletal effects: a co-twin control study.

Exercise and improved nutrition offer safe, low-cost and widely applicable approaches to potentially reduce the burden of fractures. We conducted a cross-sectional study of 30 monozygotic and 26 dizygotic male twin pairs, aged 7-20 years to test the following hypotheses: (1) Associations between bone mass and dimensions and exercise are greater than between bone mass and dimensions and protein or calcium intakes; (2) exercise or nutrient intake are associated with appendicular bone mass before puberty and axial bone mass during and after puberty. Total body and posteroanterior (PA) lumbar spine bone mineral content (BMC) and mid-femoral shaft dimensions were measured using dual energy X-ray absorptometry (DEXA). Relationships between within-pair differences in nutrient intake (determined by weighed-food diaries) or exercise duration (determined by questionnaire) and within-pair differences in BMC and bone dimensions were tested using linear regression analysis. In multivariate analyses, within-pair differences in exercise duration were associated with within-pair differences in total body, leg and spine BMC, and cortical thickness. Every-hour-per-week difference in exercise was associated with a 31-g (1.2%) difference in total body BMC, a 10-g (1.4%) difference in leg BMC, a 0.5-g difference in spine BMC and a 0.1-mm difference in cortical thickness ( p <0.01- p <0.1). A 1-g difference in protein intake was associated with a 0.8-g (0.4%) difference in arm BMC ( p <0.05). These relationships were present in peri-pubertal and post-pubertal pairs but not in pre-pubertal pairs. Exercise during growth appears to have greater skeletal benefits than variations in protein or calcium intakes, with the site-specific effects evident in more mature twins.

Regional specificity of exercise and calcium during skeletal growth in girls: a randomized controlled trial.

Combining exercise with calcium supplementation may produce additive or multiplicative effects at loaded sites; thus, we conducted a single blind, prospective, randomized controlled study in pre- and early-pubertal girls to test the following hypotheses. (1) At the loaded sites, exercise and calcium will produce greater benefits than exercise or calcium alone. (2) At non-loaded sites, exercise will have no benefit, whereas calcium with or without exercise will increase bone mass over that in exercise alone or no intervention. Sixty-six girls aged 8.8 +/- 0.1 years were randomly assigned to one of four study groups: moderate-impact exercise with or without calcium or low-impact exercise with or without calcium. All participants exercised for 20 minutes, three times a week and received Ca-fortified (434 +/- 19 mg/day) or non-fortified foods for 8.5 months. Analysis of covariance (ANCOVA) was used to determine interaction and main effects for exercise and calcium on bone mass after adjusting for baseline bone mineral content and growth in limb lengths. An exercise-calcium interaction was detected at the femur (7.1%, p < 0.05). In contrast, there was no exercise-calcium interaction detected at the tibia-fibula; however, there was a main effect of exercise: bone mineral content increased 3% more in the exercise than non-exercise groups (p < 0.05). Bone mineral content increased 2-4% more in the calcium-supplemented groups than the non-supplemented groups at the humerus (12.0% vs. 9.8%, respectively, p < 0.09) and radius-ulna (12.6% vs. 8.6%, respectively, p < 0.01). In conclusion, greater gains in bone mass at loaded sites may be achieved when short bouts of moderate exercise are combined with increased dietary calcium, the former conferring region-specific effects and the latter producing generalized effects.