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1.
BMJ Open ; 10(2): e026876, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32086348

RESUMO

OBJECTIVES: This review provides insights into the potential for aspirin to preserve bone mineral density (BMD) and reduce fracture risk, building knowledge of the risk-benefit profile of aspirin. METHODS: We conducted a systematic review and exploratory meta-analysis of observational studies. Electronic searches of MEDLINE and Embase, and a manual search of bibliographies was undertaken for studies published to 28 March 2018. Studies were included if: participants were men or women aged ≥18 years; the exposure of interest was aspirin; and relative risks, ORs and 95% CIs for the risk of fracture or difference (percentage or absolute) in BMD (measured by dual energy X-ray absorptiometry) between aspirin users and non-users were presented. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklists for observational studies. Pooled ORs for any fracture and standardised mean differences (SMDs) for BMD outcomes were calculated using random-effects models. RESULTS: Twelve studies met the inclusion criteria and were included in the meta-analysis. Aspirin use was associated with a 17% lower odds for any fracture (OR 0.83, 95% CI 0.70 to 0.99; I2=71%; six studies; n=511 390). Aspirin was associated with a higher total hip BMD for women (SMD 0.03, 95% CI -0.02 to 0.07; I2=0%; three studies; n=9686) and men (SMD 0.06, 95% CI -0.02 to 0.13, I2=0%; two studies; n=4137) although these associations were not significant. Similar results were observed for lumbar spine BMD in women (SMD 0.03, 95% CI -0.03 to 0.09; I2=34%; four studies; n=11 330) and men (SMD 0.08; 95% CI -0.01 to 0.18; one study; n=432). CONCLUSIONS: While the benefits of reduced fracture risk and higher BMD from aspirin use may be modest for individuals, if confirmed in prospective controlled trials, they may confer a large population benefit given the common use of aspirin in older people.

2.
Bone ; 130: 115085, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31622778

RESUMO

PURPOSE: Osteocalcin (OC), an osteoblast-specific secreted protein expressed by mature osteoblasts, is used in clinical practice and in research as a marker of bone turnover. The carboxylated (cOC) and undercarboxylated (ucOC) forms may have a different biological function but age-specific reference ranges for these components are not established. Given the different physiological roles, development of reference ranges may help to identify people at risk for bone disease. METHODS: Blood was collected in the morning after an overnight fast from 236 adult men (18 to 92 years old) free of diabetes, antiresorptive, warfarin or glucocorticoid use. Serum was analyzed for total osteocalcin (tOC) and the ucOC fraction using the hydroxyapatite binding method. cOC, ucOC/tOC and cOC/tOC ratios were calculated. Reference intervals were established by polynomial quantile regression analysis. RESULTS: The normal ranges for young men (≤30 years) were: tOC 17.9-56.8 ng/mL, ucOC 7.1-22.0 ng/mL, cOC 8.51-40.3 ng/mL (2.5th to 97.5th quantiles). Aging was associated with a "U" shaped pattern for tOC, cOC and ucOC levels. ucOC/tOC ratio was higher, while cOC/tOC ratio was lower in men of advanced age. Age explained ∼31%, while body mass index explained ∼4%, of the variance in the ratios. CONCLUSIONS: We have defined normal reference ranges for the OC forms in Australian men and demonstrated that the OC ratios may be better measures, than the absolute values, to identify the age-related changes on OC in men. These ratios may be incorporated into future research and clinical trials, and their associations with prediction of events, such as fracture or diabetes risk, should be determined.

3.
J Bone Miner Res ; 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31821619

RESUMO

More than 70% of women sustaining fractures have osteopenia or "normal" bone mineral density (BMD). These women remain undetected using the BMD threshold of -2.5 SD for osteoporosis. As microstructural deterioration increases bone fragility disproportionate to the bone loss producing osteopenia/normal BMD, we hypothesized that the structural fragility score (SFS) of ≥70 units, a measure capturing severe cortical and trabecular deterioration, will identify these women. Distal radial images were acquired using high-resolution peripheral quantitative tomography in postmenopausal French women, mean age 67 years (range 42-96 years); 1539 women were followed for 4 years (QUALYOR) and 561 women followed for 8 years (OFELY). Women with osteopenia or normal BMD accounted for ~80% of fractures. Women ≥70 years, 29.2% of the cohort, accounted for 39.2% to 61.5% of fractures depending on follow-up duration. Women having fractures had a higher SFS, lower BMD, and a higher fracture risk assessment score (FRAX) than women remaining fracture-free. In each BMD category (osteoporosis, osteopenia, normal BMD), fracture incidence was two to three times higher in women with SFS ≥70 than <70. In multivariable analyses, associations with fractures remained for BMD and SFS, not FRAX. BMD was no longer, or weakly, associated with fractures after accounting for SFS, whereas SFS remained associated with fracture after accounting for BMD. SFS detected two-to threefold more women having fractures than BMD or FRAX. SFS in women with osteopenia/normal BMD conferred an odds ratio for fracture of 2.69 to 5.19 for women of any age and 4.98 to 12.2 for women ≥70 years. Receiver-operator curve (ROC) analyses showed a significant area under the curve (AUC) for SFS, but not BMD or FRAX for the women ≥70 years of age. Targeting women aged ≥70 years with osteopenia indicated that treating 25% using SFS to allocate treatment conferred a cost-effectiveness ratio < USD $21,000/QALY saved. Quantifying microstructural deterioration complements BMD by identifying women without osteoporosis at imminent and longer-term fracture risk. © 2019 American Society for Bone and Mineral Research.

4.
Bone ; 128: 115039, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31437567

RESUMO

INTRODUCTION: Appendicular fractures are less common in Chinese than Caucasian women. Bone mineral density (BMD) is lower, not higher than in Caucasians because Chinese have smaller appendicular dimensions than Caucasians. However, smaller bones may offset the liability to fracture by being assembled with a more robust microstructure. We hypothesized that Chinese assemble an appendicular skeleton with a thicker, less porous and more mineralized cortex that is less deteriorated in advanced age than in Caucasians. METHODS: We compared anthropometry in 477 Chinese and 278 Caucasian women and compared bone microstructure using high-resolution peripheral quantitative computed tomography in another cohort of 186 Chinese and 381 Caucasian women aged 18 to 86 years, all living in Melbourne, Australia. Trabecular plate (p) and rod (r) bone volume/total volume (BV/TV) were quantified using individual trabecula segmentation (ITS). Bone strength was estimated using micro-finite element analysis (µFEA). RESULTS: Premenopausal Chinese were shorter than Caucasian women, mainly due to shorter leg length. Distal radial total cross sectional area (CSA) was 14.8% smaller (p < 0.001). After adjusting for age and total CSA, Chinese had similar cortical and medullary areas but 0.30 SD lower cortical porosity and 0.27 SD higher matrix mineral density (both p < 0.05). Trabecular plate-to-rod ratio was 0.55 SD higher due to a 0.41 SD higher pBV/TV and 0.36 SD lower rBV/TV (p ranging 0.001 to 0.023). Chinese also had 0.36 SD greater whole bone stiffness and 0.36 SD greater failure load than Caucasians (both p < 0.05). After adjusting for age and total CSA, postmenopausal Chinese had 3.3% smaller cortical area, medullary area was 2.1% larger, cortical porosity was no lower, matrix mineral density and pBV/TV were no higher compared with Caucasians at the distal radius. Whole bone stiffness was 0.39 SD lower and failure load was 0.40 SD lower in Chinese (both p < 0.05). CONCLUSION: Chinese build a more robust skeleton than Caucasians during growth, an advantage not observed in advanced age due to greater bone loss or race-specific secular trends in bone morphology.

5.
JBMR Plus ; 3(4): e10078, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31044180

RESUMO

Absolute values of cortical porosity and trabecular density are used to estimate fracture risk, but these values are the net result of their growth-related assembly and age-related deterioration. Because bone loss affects both cortical and trabecular bone, we hypothesized that a surrogate measure of bone fragility should capture the age-related deterioration of both traits, and should do so independently of their peak values. Accordingly, we developed a structural fragility score (SFS), which quantifies the increment in distal radial cortical porosity and decrement in trabecular density relative to their premenopausal mean values in 99 postmenopausal women with forearm fractures and 105 controls using HR-pQCT. We expressed the results as odds ratios (ORs; 95% CI). Cortical porosity was associated with fractures in the presence of deteriorated trabecular density (OR 2.30; 95% CI, 1.30 to 4.05; p = 0.004), but not if trabecular deterioration was absent (OR 0.96; 95% CI, 0.50 to 1.86; p = 0.91). Likewise, trabecular density was associated with fractures in the presence of high cortical porosity (OR 3.35; 95% CI, 1.85 to 6.07; p < 0.0001), but not in its absence (OR 1.60; 95% CI, 0.78 to 3.28; p = 0.20). The SFS, which captures coexisting cortical and trabecular deterioration, was associated with fractures (OR 4.52; 95% CI, 2.17 to 9.45; p < 0.0001). BMD was associated with fracture before accounting for the SFS (OR 5.79; 95% CI, 1.24 to 27.1; p = 0.026), not after (OR 4.38; 95% CI, 0.48 to 39.9; p = 0.19). The SFS was associated with fracture before (OR 4.67; 95% CI, 2.21 to 9.88) and after (OR 3.94; 95% CI, 1.80 to 8.6) accounting for BMD (both ps < 0.0001). The disease of bone fragility is captured by cortical and trabecular deterioration: A measurement of coexisting cortical and trabecular deterioration is likely to identify women at risk for fracture more robustly than absolute values of cortical porosity, trabecular density, or BMD. © 2018 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

6.
J Bone Miner Res ; 34(8): 1451-1460, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30883870

RESUMO

Advancing age is accompanied by a reduction in bone formation and remodeling imbalance, which produces microstructural deterioration. This may be partly caused by a diversion of mesenchymal cells towards adipocytes rather than osteoblast lineage cells. We hypothesized that microstructural deterioration would be associated with an increased marrow adiposity, and each of these traits would be independently associated with nonvertebral fractures and improve discrimination of women with fractures from controls over that achieved by femoral neck (FN) areal bone mineral density (aBMD) alone. The marrow adiposity and bone microstructure were quantified from HR-pQCT images of the distal tibia and distal radius in 77 women aged 40 to 70 years with a recent nonvertebral fracture and 226 controls in Melbourne, Australia. Marrow fat measurement from HR-pQCT images was validated using direct histologic measurement as the gold standard, at the distal radius of 15 sheep, with an agreement (R2 = 0.86, p < 0.0001). Each SD higher distal tibia marrow adiposity was associated with 0.33 SD higher cortical porosity, and 0.60 SD fewer, 0.24 SD thinner, and 0.72 SD more-separated trabeculae (all p < 0.05). Adjusted for age and FN aBMD, odds ratios (ORs) (95% CI) for fracture per SD higher marrow adiposity and cortical porosity were OR, 3.39 (95% CI, 2.14 to 5.38) and OR, 1.79 (95% CI, 1.14 to 2.80), respectively. Discrimination of women with fracture from controls improved when cortical porosity was added to FN aBMD and age (area under the receiver-operating characteristic curve [AUC] 0.778 versus 0.751, p = 0.006) or marrow adiposity was added to FN aBMD and age (AUC 0.825 versus 0.751, p = 0.002). The model including FN aBMD, age, cortical porosity, trabecular thickness, and marrow adiposity had an AUC = 0.888. Results were similar for the distal radius. Whether marrow adiposity and cortical porosity indices improve the identification of women at risk for fractures requires validation in prospective studies. © 2019 American Society for Bone and Mineral Research.

7.
J Nutr Sci ; 8: e10, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30918631

RESUMO

CVD is common in older adults. Consumption of 'meat' (beef, pork, lamb, game, poultry, seafood, eggs) and dairy foods (milk, cheese, yoghurt) is encouraged in older adults as these foods provide protein and nutrients such as essential fatty acids, Ca, Fe, Zn and vitamins A, D and B12 required for healthy ageing. However, these foods also contain saturated fats considered detrimental to cardiovascular health. To determine the effect of their consumption on CVD risk we assessed associations between fat intake from 'meat' and dairy foods and serum cholesterol levels in 226 aged-care residents (mean age 85·5 years, 70 % female). Dietary intake was determined over 2 d using visual estimation of plate waste. Fat content of foods was determined using nutrition analysis software (Xyris, Australia). Fasting serum total cholesterol (TC), LDL-cholesterol and HDL-cholesterol were measured, and the TC:HDL-cholesterol ratio calculated. Associations were determined using random-effect models adjusted for CVD risk factors using STATA/IC 13.0. Total fat and saturated fat from 'meat' and dairy foods were associated with higher serum HDL-cholesterol levels, and dairy fat intake and number of servings were associated with a lower TC:HDL-cholesterol ratio. Every 10 g higher intake of fat and saturated fat from dairy products, and each additional serving was associated with a -0·375 (95 % CI -0·574, -0·175; P = 0·0002), a -0·525 (95 % CI -0·834, -0·213; P = 0·001) and a -0·245 (95 % CI -0·458, -0·033; P = 0·024) lower TC:HDL-cholesterol ratio, respectively. Provision of dairy foods and 'meat' in recommended amounts to institutionalised older adults potentially improves intakes of key nutrients with limited detriment to cardiovascular health.


Assuntos
Colesterol/efeitos adversos , Colesterol/sangue , Laticínios/efeitos adversos , Gorduras na Dieta/efeitos adversos , Carne/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Austrália , Doenças Cardiovasculares , Sistema Cardiovascular , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos Transversais , Dieta , Ácidos Graxos/efeitos adversos , Feminino , Instituição de Longa Permanência para Idosos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
8.
Nat Rev Rheumatol ; 15(4): 225-236, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30755735

RESUMO

Bone volume, microstructure and its material composition are maintained by bone remodelling, a cellular activity carried out by bone multicellular units (BMUs). BMUs are focally transient teams of osteoclasts and osteoblasts that respectively resorb a volume of old bone and then deposit an equal volume of new bone at the same location. Around the time of menopause, bone remodelling becomes unbalanced and rapid, and an increased number of BMUs deposit less bone than they resorb, resulting in bone loss, a reduction in bone volume and microstructural deterioration. Cortices become porous and thin, and trabeculae become thin, perforated and disconnected, causing bone fragility. Antiresorptive agents reduce fracture risk by reducing the rate of bone remodelling so that fewer BMUs are available to remodel bone. Bone fragility is not abolished by these drugs because existing microstructural deterioration is not reversed, unsuppressed remodelling continues producing microstructural deterioration and unremodelled bone that becomes more mineralized can become brittle. Anabolic agents reduce fracture risk by stimulating new bone formation, which partly restores bone volume and microstructure. To guide fracture prevention, this Review provides an overview of the structural basis of bone fragility, the mechanisms of remodelling and how anabolic and antiresorptive agents target remodelling defects.


Assuntos
Anabolizantes/uso terapêutico , Desmineralização Patológica Óssea/prevenção & controle , Conservadores da Densidade Óssea/uso terapêutico , Animais , Desmineralização Patológica Óssea/terapia , Remodelação Óssea/efeitos dos fármacos , Reabsorção Óssea/tratamento farmacológico , Humanos
9.
J Bone Miner Res ; 34(4): 616-625, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30615801

RESUMO

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.

10.
J Bone Miner Res ; 34(1): 49-58, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30138543

RESUMO

In mice, glucocorticoid-induced insulin resistance occurs largely through impaired osteoblast function and decreased circulating undercarboxylated osteocalcin (ucOC). Whether these mechanisms contribute to glucocorticoid-induced insulin resistance in humans has yet to be established. In addition, the effects of glucocorticoids on the exercise-induced increase in circulating ucOC and insulin sensitivity are also unknown. We hypothesized that acute glucocorticoid treatment would lead to basal and postexercise insulin resistance in part through decreased circulating ucOC and ucOC-mediated skeletal muscle protein signaling. Nine healthy men completed two separate cycling sessions 12 hours after ingesting either glucocorticoid (20 mg prednisolone) or placebo (20 mg Avicel). The homeostatic model assessment was used to assess basal insulin sensitivity and a 2-hour euglycemic-hyperinsulinemic clamp was commenced 3 hours after exercise to assess postexercise insulin sensitivity. Serum ucOC and skeletal muscle protein signaling were measured. Single-dose glucocorticoid ingestion increased fasting glucose (27%, p < 0.01) and insulin (83%, p < 0.01), and decreased basal insulin sensitivity (-47%, p < 0.01). Glucocorticoids reduced insulin sensitivity after cycling exercise (-34%, p < 0.01), reduced muscle GPRC6A protein content (16%, p < 0.05), and attenuated protein phosphorylation of mTORSer2481 , AktSer374 , and AS160Thr642 (59%, 61%, and 50%, respectively; all ps < 0.05). Serum ucOC decreased (-24%, p < 0.01) which correlated with lower basal insulin sensitivity (r = 0.54, p = 0.02), lower insulin sensitivity after exercise (r = 0.72, p < 0.05), and attenuated muscle protein signaling (r = 0.48-0.71, p < 0.05). Glucocorticoid-induced basal and postexercise insulin resistance in humans is associated with the suppression of circulating ucOC and ucOC-linked protein signaling in skeletal muscle. Whether ucOC treatment can offset glucocorticoid-induced insulin resistance in human subjects requires further investigation. © 2018 American Society for Bone and Mineral Research.

11.
Artigo em Inglês | MEDLINE | ID: mdl-30237785

RESUMO

The prevalence of fragility fractures increases as longevity increases the proportion of the elderly in the community. Until recently, the majority of studies have targeted women with osteoporosis defined as a bone mineral density (BMD) T score of < -2.5 SD, despite evidence that the population burden of fractures arises from women with osteopenia. Antiresorptive agents reduce vertebral and hip fracture risk by ~50 percent during 3 years but efficacy against non-vertebral fractures, 80% of all fractures in the community, is reported in few studies, and of those, the risk reduction is only 20-30%. Recent advances in the use of antiresorptives and anabolic agents has addressed some of these unmet needs. Zoledronic acid is now reported to reduce vertebral and non-vertebral fractures rates in women with osteopenia. Studies using teriparatide demonstrate better vertebral and clinical (symptomatic vertebral and non-vertebral) antifracture efficacy than risedronate. Abaloparatide, a peptide sharing amino acid sequences with teriparatide, reduces vertebral and non-vertebral fractures. Romosozumab, a monoclonal antibody suppressing sclerostin, reduces vertebral and non-vertebral fractures within a year of starting treatment, and does so more greatly than alendronate. Some recent studies signal undesirable effects of therapy but provide essential cautionary insights into long term management. Cessation of denosumab is associated with a rapid increase in bone remodeling and the uncommon but clinically important observation of increased multiple vertebral fractures suggesting the need to start alternative anti-resorptive therapy around the time of stopping denosumab. Antiresorptives like bisphosphonates and denosumab suppress remodeling but not completely. Antifracture efficacy may be limited, in part, as a consequence of continued unsuppressed remodeling, particularly in cortical bone. Bisphosphonates may not distribute in deeper cortical bone, so unbalanced intracortical remodeling continues to cause microstructural deterioration. In addition, suppressed remodeling may compromise the material composition by increasing matrix mineral density and glycosylation of collagen. As antiresorptive agents do not restore microstructural deterioration existing at the time of starting treatment, under some circumstances, anabolic therapy may be more appropriate first line treatment. Combining antiresorptive and anabolic therapy is an alternative but whether anti-fracture efficacy is greater than that achieved by either treatment alone is not known.

12.
Curr Osteoporos Rep ; 16(5): 561-572, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30187285

RESUMO

PURPOSE OF REVIEW: Bone densitometry provides a two-dimensional projected areal apparent bone mineral density that fails to capture the heterogeneity of bone's material composition and macro-, micro-, and nano-structures critical to its material and structural strength. Assessment of the structural basis of bone fragility has focused largely on trabecular bone based on the common occurrence of fragility fractures at sites with substantial amounts of trabecular bone. This review focuses on the contribution of cortical bone to bone fragility throughout life. RECENT FINDINGS: Accurately differentiating cortical and trabecular bone loss has important implications in quantifying bone fragility as these compartments have differing effects on bone strength. Recent advances in imaging methodology have improved distinction of these two compartments by (i) recognition of a cortico-trabecular transitional zone and (ii) quantifying bone microstructure in a region of interest that is a percentage of bone length rather than a fixed point. Additionally, non-invasive three-dimensional imaging methods allow more accurate quantification of changes in the cortical, trabecular, and cortico-trabecular compartments during growth, aging, disease, and treatment. Over 75% of the skeleton is assembled as cortical bone. Of all fragility fractures, ~ 80% are appendicular and involve regions rich in cortical bone and ~ 70% of all age-related appendicular bone loss is cortical and is mainly due to unbalanced intracortical remodeling which increases cortical porosity. The failure to achieve the optimal peak bone microstructure during growth due to disease and the deterioration in cortical and trabecular bone produced by bone loss compromise bone strength. The loss of strength produced by microstructural deterioration is disproportionate to the bone loss producing this deterioration. The reason for this is that the loss of strength increases as a 7th power function of the rise in cortical porosity and a 3rd power function of the fall in trabecular density (Schaffler and Burr in J Biomech. 21(1):13-6, 1988), hence the need to quantify bone microstructure.


Assuntos
Envelhecimento , Desenvolvimento Ósseo , Osso Esponjoso/diagnóstico por imagem , Osso Cortical/diagnóstico por imagem , Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/fisiopatologia , Densidade Óssea , Remodelação Óssea , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/fisiopatologia , Osso e Ossos/ultraestrutura , Osso Esponjoso/fisiopatologia , Osso Esponjoso/ultraestrutura , Osso Cortical/fisiopatologia , Osso Cortical/ultraestrutura , Humanos , Imagem Tridimensional , Osteoporose/fisiopatologia , Porosidade
13.
Bone ; 114: 298-303, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30008396

RESUMO

The diagnostic threshold for osteoporosis, a bone mineral density (BMD) T-score ≤ -2.5, signals an increased risk for fracture. However, most fragility fractures arise among the majority of women with 'osteopenia' or 'normal' BMD. We hypothesized that a BMD T-score of -2.5, even if not intended as a treatment threshold, paradoxically may create disincentive to initiating treatment of women with osteopenia or normal BMD at high risk for fracture. From a population-based BMD registry covering the Province of Manitoba, Canada, we identified 3735 untreated women aged ≥ 50 years undergoing BMD screening in 2006-2015 found to qualify for Osteoporosis Canada guidelines-based treatment. The main outcome was prescription of an approved osteoporosis medications in the year after BMD testing ascertained from a population-based pharmacy database. We estimated adjusted odds ratios (OR, 95% confidence interval [CI]) for treatment initiation based on BMD, major fracture history (non-traumatic vertebral, hip or multiple fractures), age, and calendar year (to examine the impact of treatment guidelines published in 2010). Among these women, 50% (1853) initiated treatment: 71% with osteoporosis, 21% with osteopenia, and 5% with normal BMD with similar values in those with a prior major fracture (71%, 19%, 5%, respectively). Compared to women with osteoporosis, adjusted ORs for treatment of high risk women with osteopenia or normal BMD alone were 0.10 (95% CI 0.09-0.12) and 0.02 (95% CI 0.01-0.04), respectively, and no higher in women with a prior major fracture (OR 1.00, 95% CI 0.84-1.19) or following introduction of treatment guidelines (p = 0.294). In summary, we found evidence that the diagnostic threshold for osteoporosis may serve as a disincentive to initiation of treatment in many women at high risk for incident fracture.


Assuntos
Densidade Óssea/fisiologia , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/epidemiologia , Osteoporose/diagnóstico por imagem , Osteoporose/epidemiologia , Sistema de Registros , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico , Estudos de Coortes , Feminino , Fraturas Ósseas/prevenção & controle , Humanos , Manitoba/epidemiologia , Pessoa de Meia-Idade , Osteoporose/tratamento farmacológico , Fatores de Risco
14.
J Bone Miner Res ; 33(11): 1948-1955, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30001459

RESUMO

Distal forearm fractures during growth are more common in males than females. Because metaphyseal cortical bone is formed by coalescence of trabeculae emerging from the periphery of the growth plate, we hypothesized that the later onset of puberty in males produces a longer delay in trabecular bone formation and coalescence, which leaves a transient phase of high cortical porosity, low matrix mineral density, and high trabecular density relative to females. We quantified the nondominant distal radial microstructure using high-resolution peripheral quantitative computed tomography in 214 healthy Chinese boys and 219 Chinese girls aged between 7 and 17 years living in Hong Kong. Measurements of 110 slices (9.02 mm) were acquired 5 mm proximal to the growth plate of the nondominant distal radius. Porosity was measured using StrAx1.0 (Straxcorp, Melbourne, VIC, Australia) and trabecular plate and rod structure were measured using individual trabecula segmentation (ITS). Mechanical properties were estimated using finite element analysis (FEA). Results were adjusted for age, total bone cross-sectional area (CSA), dietary calcium intake, and physical activity. In boys, total bone CSA was 17.2% to 22.9% larger throughout puberty, cortical/total bone CSA was 5.1% smaller in Tanner stage 2 only, cortical porosity was 9.4% to 17.5% higher, and matrix mineral density was 1.0% to 2.5% lower in Tanner stage 2 to 5, than girls. Boys had higher trabecular rod BV/TV in Tanner stage 3 and 4, but higher trabecular plate BV/TV and plate to rod ratio in Tanner stage 5, than girls. Boys had 17.0% lower apparent modulus than girls in Tanner stage 2. A transient phase of higher porosity due to dissociation between bone mineral accrual and linear growth may contribute to higher distal radial bone fragility in Chinese boys compared to girls. © 2018 American Society for Bone and Mineral Research.


Assuntos
Grupo com Ancestrais do Continente Asiático , Osso Esponjoso/anatomia & histologia , Osso Cortical/anatomia & histologia , Puberdade/fisiologia , Caracteres Sexuais , Adolescente , Fenômenos Biomecânicos , Criança , Feminino , Humanos , Estilo de Vida , Masculino , Tamanho do Órgão
15.
J Bone Miner Res ; 33(11): 1999-2006, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29920773

RESUMO

Advancing age and reduced loading are associated with a reduction in bone formation. Conversely, loading increases periosteal apposition and may reduce remodeling imbalance and slow age-related bone loss, an important outcome for the proximal femur, which is a common site of fracture. The ability to take advantage of bone's adaptive response to increase bone strength has been hampered by a lack of knowledge of which exercises and specific leg muscles load the superior femoral neck: a common region of microcrack initiation and progression following a sideways fall. We used an in vivo method of quantifying focal strains within the femoral neck in postmenopausal women during walking, stair ambulation, and jumping. Relative to walking, stair ambulation and jumping induced significantly higher strains in the anterior and superior aspects of the femoral neck, common regions of microcrack initiation and progression following a fall. The gluteus maximus, a hip extensor muscle, induced strains in the femoral neck during stair ambulation and jumping, in contrast to walking which induced strains via the iliopsoas, a hip flexor. The ground reaction force was closely associated with the level of strain during each task, providing a surrogate indicator of the potential for a given exercise to load the femoral neck. The gluteal muscles combined with an increased ground reaction force relative to walking induce high focal strains within the anterosuperior region of the femoral neck and therefore provide a target for exercise regimens designed to slow bone loss and maintain or improve microstructural strength. Model files used for calculating femoral neck strains are available at uitbl.mechse.illinois.edu/downloads © 2018 American Society for Bone and Mineral Research.


Assuntos
Colo do Fêmur/fisiologia , Locomoção/fisiologia , Idoso , Fenômenos Biomecânicos , Marcha/fisiologia , Humanos , Pessoa de Meia-Idade , Fatores de Tempo , Suporte de Carga
16.
J Bone Miner Res ; 33(7): 1312-1317, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29489033

RESUMO

Reduced bone mineral density (BMD) may be due to reduced mineralized bone matrix volume, incomplete secondary mineralization, or reduced primary mineralization. Because bone biopsy is invasive, we hypothesized that noninvasive image acquisition at high resolution can accurately quantify matrix mineral density (MMD). Quantification of MMD was confined to voxels attenuation photons above 80% of that produced by fully mineralized bone matrix because attenuation at this level is due to variation in mineralization, not porosity. To assess accuracy, 9 cadaveric distal radii were imaged at a voxel size of 82 microns using high-resolution peripheral quantitative computed tomography (HR-pQCT; XtremeCT, Scanco Medical AG, Bruttisellen, Switzerland) and compared with VivaCT 40 (µCT) at 19-micron voxel size. Associations between MMD and porosity were studied in 94 healthy vitamin D-replete premenopausal women, 77 postmenopausal women, and in a 27-year-old woman with vitamin D-dependent rickets (VDDR). Microstructure and MMD were quantified using StrAx (StraxCorp, Melbourne, Australia). MMD measured by HR-pQCT and µCT correlated (R = 0.87; p < 0.0001). The precision error for MMD was 2.43%. Cortical porosity and MMD were associated with age (r2 = 0.5 and -0.4, respectively) and correlated inversely in pre- and postmenopausal women (both r2 = 0.9, all p < 0.001). Porosity was higher, and MMD was lower, in post- than in premenopausal women (porosity 40.3% ± 7.0 versus 34.7% ± 3.5, respectively; MMD 65.4% ± 1.8 versus 66.6% ± 1.4, respectively, both p < 0.001). In the woman with VDDR, MMD was 5.6 SD lower and porosity was 5.6 SD higher than the respective trait means in premenopausal women. BMD was reduced (Z-scores femoral neck -4.3 SD, lumbar spine -3.8 SD). Low-radiation HR-pQCT may facilitate noninvasive quantification of bone's MMD and microstructure in health, disease, and during treatment. © 2018 American Society for Bone and Mineral Research.


Assuntos
Densidade Óssea , Matriz Óssea/fisiopatologia , Osso Cortical/fisiopatologia , Pós-Menopausa/fisiologia , Pré-Menopausa/fisiologia , Raquitismo/tratamento farmacológico , Raquitismo/fisiopatologia , Vitamina D/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Matriz Óssea/diagnóstico por imagem , Osso Cortical/diagnóstico por imagem , Feminino , Humanos , Pessoa de Meia-Idade , Porosidade , Rádio (Anatomia)/diagnóstico por imagem , Rádio (Anatomia)/patologia , Rádio (Anatomia)/fisiopatologia , Raquitismo/diagnóstico por imagem , Adulto Jovem
17.
J Am Med Dir Assoc ; 19(1): 33-39, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29174562

RESUMO

OBJECTIVE: Although it has been established that sufficient protein is required to maintain good nutritional status and support healthy aging, it is not clear if the pattern of protein consumption may also influence nutritional status, especially in institutionalized elderly who are at risk of malnutrition. Therefore, we aim to determine the association between protein intake distribution and nutritional status in institutionalized elderly people. DESIGN: Cross-sectional study among 481 institutionalized older adults. METHODS: Dietary data from 481 ambulant elderly people (68.8% female, mean age 87.5 ± 6.3 years) residing in 52 aged-care facilities in Victoria, Australia, were assessed over 2 days using plate waste analysis. Nutritional status was determined using the Mini-Nutritional Assessment tool and serum (n = 208) analyzed for albumin, hemoglobin, and IGF-1. Protein intake distribution was classified as: spread (even distribution across 3 meals, n = 65), pulse (most protein consumed in one meal, n = 72) or intermediate (n = 344). Regression analysis was used to investigate associations. RESULTS: Mean protein intakes were higher in the spread (60.5 ± 2.0 g/d) than intermediate group (56.0 ± 0.8 g/d, P = .037), and tended to be higher than those in the pulse group (55.9 ± 1.9 g/d, P = .097). Residents with an even distribution of protein intake achieved a higher level of the recommended daily intake for protein (96.2 ± 30.0%) than the intermediate (86.3 ± 26.2%, P = .008) and pulse (87.4 ± 30.5%, P = .06) groups, and also achieved a greater level of their estimated energy requirements (intermediate; P = .039, pulse; P = .001). Nutritional status (Mini-Nutritional Assessment score) did not differ between groups (pulse; 20.5 ± 4.5, intermediate; 21.0 ± 2.5, spread; 20.5 ± 3.5), nor did any other indices of nutritional status. CONCLUSIONS: Meeting protein requirements is required before protein distribution may influence nutritional status in institutionalized elderly. Achieving adequate protein and energy intakes is more likely when protein is distributed evenly throughout the day. Provision of high protein foods especially at breakfast, and in the evening, may support protein adequacy and healthy aging, especially for institutionalized elderly.


Assuntos
Proteínas na Dieta/administração & dosagem , Ingestão de Energia , Desnutrição/prevenção & controle , Assistência Centrada no Paciente/métodos , Qualidade de Vida , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Austrália , Estudos Transversais , Feminino , Avaliação Geriátrica , Instituição de Longa Permanência para Idosos/estatística & dados numéricos , Humanos , Masculino , Casas de Saúde/estatística & dados numéricos , Avaliação Nutricional , Necessidades Nutricionais , Fatores Sexuais
18.
J Bone Miner Res ; 33(4): 598-605, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29218771

RESUMO

After menopause, remodeling becomes unbalanced and rapid. Each of the many remodeling transactions deposits less bone than it resorbed, producing microstructural deterioration. Trabecular bone is said to be lost more rapidly than cortical bone. However, because 80% of the skeleton is cortical, we hypothesized that most menopause-related bone loss and changes in bone microstructure are cortical, not trabecular in origin, and are the result of intracortical remodeling. Distal tibial and distal radial microstructure were quantified during 3.1 years (range, 1.5 to 4.5 years) of follow-up using high-resolution peripheral quantitative computed tomography and StrAx software in 199 monozygotic and 125 dizygotic twin pairs aged 25 to 75 years in Melbourne, Australia. The annual increases in tibial cortical porosity accelerated, being 0.44%, 0.80%, and 1.40% in women remaining premenopausal, transitioning to perimenopause, and from perimenopausal to postmenopause, respectively. Porosity increased in the compact-appearing, outer, and inner transitional zones of the cortex (all p < 0.001). The annual decrease in trabecular bone volume/tissue volume (BV/TV) also accelerated, being 0.17%, 0.26%, and 0.31%, respectively. Little bone loss was observed before menopause. The reduction in BV/TV was due to a decrease in trabecular number (p < 0.001). The greatest bone loss, 7.7 mg hydroxyapatite (HA) annually, occurred in women transitioning from perimenopausal to postmenopause and of this, 6.1 mg HA (80%) was cortical. Results were similar for the distal radius. Despite microarchitectural changes, no significant bone loss was observed before menopause. Over 90% of appendicular bone loss occurs during and after menopause, over 80% is cortical, and this may explain why 80% of fractures are appendicular. © 2017 American Society for Bone and Mineral Research.


Assuntos
Osso Cortical , Menopausa/metabolismo , Osteoporose Pós-Menopausa , Software , Tomografia Computadorizada por Raios X , Gêmeos Dizigóticos , Adulto , Idoso , Osso Cortical/diagnóstico por imagem , Osso Cortical/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/diagnóstico por imagem , Osteoporose Pós-Menopausa/metabolismo , Gêmeos Monozigóticos
19.
Bone ; 103: 131-135, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28673637

RESUMO

BACKGROUND: In premenopausal women with early estrogen-receptor-positive breast cancer, combined ovarian suppression and aromatase inhibition reduce estradiol production precipitously. The resulting unbalanced and rapid bone remodelling replaces older bone with less bone that is less fully mineralized. We hypothesized that these changes result in severe microstructural deterioration and reduced matrix mineralization density. METHODS: Images of the distal radius and distal tibia were acquired using high-resolution peripheral quantitative computed tomography in a cross-sectional study of 27 premenopausal women, mean age 43.3years (range 30.4 to 53.7) with early breast cancer made estradiol deficient for 17months (range 6-120) using ovarian suppression and aromatase inhibition, 42 healthy age-matched premenopausal and 35 postmenopausal controls, mean age 62.6years (range 60.2 to 65.5). Cortical and trabecular microstructure were quantified using Strax software. RESULTS: Compared with premenopausal controls, the women with breast cancer had 0.75 SD (95% CI 0.21 to 1.29) lower distal radial trabecular bone volume due to 1.29 SD (0.71 to 1.87) fewer trabeculae. Cortical porosity was 1.25 SD (0.59 to 1.91) higher but cortical thickness was not reduced. Compared with postmenopausal controls 20years older, cases had comparable or lower trabecular bone volume and comparable cortical porosity and thickness. Matrix mineral density was 1.56 SD (0.90 to 2.22) lower than in premenopausal controls and 2.17 SD (1.50 to 2.84) lower than in postmenopausal controls. Results at the tibia were similar. CONCLUSION: The severe cortical porosity and trabecular deterioration associated with estradiol depletion and the longevity of premenopausal women with early breast cancer treated with endocrine therapy provide a compelling rationale to investigate the efficacy of antiresorptive therapy initiated at the time of breast cancer treatment.


Assuntos
Osso e Ossos/patologia , Neoplasias da Mama/tratamento farmacológico , Moduladores de Receptor Estrogênico/efeitos adversos , Adulto , Idoso , Osso e Ossos/efeitos dos fármacos , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Ovariectomia , Pré-Menopausa
20.
Bone ; 101: 206-213, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28502884

RESUMO

INTRODUCTION: Individuals differ in forearm length. As microstructure differs along the radius, we hypothesized that errors may occur when sexual and racial dimorphisms are quantified at a fixed distance from the radio-carpal joint. METHODS: Microstructure was quantified ex vivo in 18 cadaveric radii using high resolution peripheral quantitative computed tomography and in vivo in 158 Asian and Caucasian women and men at a fixed region of interest (ROI), a corrected ROI positioned at 4.5-6% of forearm length and using the fixed ROI adjusted for cross sectional area (CSA), forearm length or height. Secular effects of age were assessed by comparing 38 younger and 33 older women. RESULTS: Ex vivo, similar amounts of bone mass fashioned adjacent cross sections. Larger distal cross sections had thinner porous cortices of lower matrix mineral density (MMD), a larger medullary CSA and higher trabecular density. Smaller proximal cross-sections had thicker less porous cortices of higher MMD, a small medullary canal with little trabecular bone. Taller persons had more distally positioned fixed ROIs which moved proximally when corrected. Shorter persons had more proximally positioned fixed ROIs which moved distally when corrected, so dimorphisms lessened. In the corrected ROIs, in Caucasians, women had 0.6 SD higher porosity and 0.6 SD lower trabecular density than men (p<0.01). In Asians, women had 0.25 SD higher porosity (NS) and 0.5 SD lower trabecular density than men (p<0.05). In women, Asians had 0.8 SD lower porosity and 0.3 SD higher trabecular density than Caucasians (p<0.01). In men, Asians and Caucasians had similar porosity and trabecular density. Results were similar using an adjusted fixed ROI. Adjusting for secular effects of age on forearm length resulted in the age-related increment in porosity increasing from 2.08 SD to 2.48 SD (p<0.05). CONCLUSION: Assessment of sex, race and age related differences in microstructure requires measurement of anatomically equivalent regions.


Assuntos
Densidade Óssea/fisiologia , Osso e Ossos/anatomia & histologia , Osso e Ossos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Osso e Ossos/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Adulto Jovem
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