Sandra Iuliano-Burns

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.

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.

Timing and magnitude of peak height velocity and peak tissue velocities for early, average, and late maturing boys and girls

Height, weight, and tissue accrual were determined in 60 male and 53 female adolescents measured annually over six years using standard anthropometry and dual‐energy X‐ray absorptiometry (DXA). Annual velocities were derived, and the ages and magnitudes of peak height and peak tissue velocities were determined using a cubic spline fit to individual data. Individuals were rank ordered on the basis of sex and age at peak height velocity (PHV) and then divided into quartiles: early (lowest quartile), average (middle two quartiles), and late (highest quartile) maturers. Sex‐ and maturity‐related comparisons in ages and magnitudes of peak height and peak tissue velocities were made. Males reached peak velocities significantly later than females for all tissues and had significantly greater magnitudes at peak. The age at PHV was negatively correlated with the magnitude of PHV in both sexes. At a similar maturity point (age at PHV) there were no differences in weight or fat mass among maturity groups in both sexes. Late maturing males, however, accrued more bone mineral and lean mass and were taller at the age of PHV compared to early maturers. Thus, maturational status (early, average, or late maturity) as indicated by age at PHV is inversely related to the magnitude of PHV in both sexes. At a similar maturational point there are no differences between early and late maturers for weight and fat mass in boys and girls. Am. J. Hum. Biol. 13:1–8, 2001.

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.

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.

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

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.

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.

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.

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.

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.