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BACKGROUND: Computed tomography (CT) captures the quantity, density, and distribution of subcutaneous and visceral (SAT and VAT) adipose tissue compartments. These metrics may change with age and sex. OBJECTIVE: The study aims to provide age-, sex-, and vertebral level-specific reference values for SAT on chest CT and for SAT and VAT on abdomen CT. MATERIALS AND METHODS: This secondary analysis of an observational study describes SAT and VAT measurements in participants of the Framingham Heart Study without known cancer diagnosis who underwent at least 1 of 2 CT examinations between 2002 and 2011. We used a previously validated machine learning-assisted pipeline and rigorous quality assurance to segment SAT at the fifth, eighth, and tenth thoracic vertebra (T5, T8, T10) and SAT and VAT at the third lumbar vertebra (L3). For each metric, we measured cross-sectional area (cm2) and mean attenuation (Hounsfield units [HU]) and calculated index (area/height2) (cm2/m2) and gauge (attenuation × index) (HU × cm2/m2). We summarized body composition metrics by age and sex and modeled sex-, age-, and vertebral level-specific reference curves. RESULTS: We included 14,898 single-level measurements from up to 4 vertebral levels of 3797 scans of 3730 Framingham Heart Study participants (1889 [51%] male with a mean [standard deviation] age of 55.6 ± 10.6 years; range, 38-81 years). The mean VAT index increased with age from 65 (cm2/m2) in males and 29 (cm2/m2) in females in the <45-year-old age group to 99 (cm2/m2) in males and 60 (cm2/m2) in females in >75-year-old age group. The increase of SAT with age was less pronounced, resulting in the VAT/SAT ratio increasing with age. A free R package and online interactive visual web interface allow access to reference values. CONCLUSIONS: This study establishes age-, sex-, and vertebral level-specific reference values for CT-assessed SAT at vertebral levels T5, T8, T10, and L3 and VAT at vertebral level L3.
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BACKGROUND: Loss of muscle mass is a known feature of sarcopenia and predicts poor clinical outcomes. Although muscle metrics can be derived from routine computed tomography (CT) images, sex-specific reference values at multiple vertebral levels over a wide age range are lacking. OBJECTIVE: The aim of this study was to provide reference values for skeletal muscle mass and attenuation on thoracic and abdominal CT scans in the community-based Framingham Heart Study cohort to aid in the identification of sarcopenia. MATERIALS AND METHODS: This secondary analysis of a prospective trial describes muscle metrics by age and sex for participants from the Framingham Heart Study without prior history of cancer who underwent at least 1 CT scan between 2002 and 2011. Using 2 previously validated machine learning algorithms followed by human quality assurance, skeletal muscle was analyzed on a single axial CT image per level at the 5th, 8th, 10th thoracic, and 3rd lumbar vertebral body (T5, T8, T10, L3). Cross-sectional muscle area (cm 2 ), mean skeletal muscle radioattenuation (SMRA, in Hounsfield units), skeletal muscle index (SMI, in cm 2 /m 2 ), and skeletal muscle gauge (SMRA·SMI) were calculated. Measurements were summarized by age group (<45, 45-54, 55-64, 65-74, ≥75 years), sex, and vertebral level. Models enabling the calculation of age-, sex-, and vertebral-level-specific reference values were created and embedded into an open access online Web application. RESULTS: The cohort consisted of 3804 participants (1917 [50.4%] males; mean age, 55.6 ± 11.8 years; range, 33-92 years) and 7162 CT scans. Muscle metrics qualitatively decreased with increasing age and female sex. CONCLUSIONS: This study established age- and sex-specific reference values for CT-based muscle metrics at thoracic and lumbar vertebral levels. These values may be used in future research investigating the role of muscle mass and attenuation in health and disease, and to identify sarcopenia.
Assuntos
Sarcopenia , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Sarcopenia/diagnóstico por imagem , Sarcopenia/complicações , Sarcopenia/patologia , Valores de Referência , Estudos Transversais , Estudos Prospectivos , Músculo Esquelético/diagnóstico por imagem , Estudos Longitudinais , Tomografia Computadorizada por Raios X/métodos , Estudos RetrospectivosRESUMO
To understand whether the bone loss which occurs after vertical sleeve gastrectomy increases the risk of fracture, we used an engineering model to estimate risk in participants before and after surgery. We found that estimated risk decreased 1 year after surgery and remained lower, though had rebounded, at year 2. PURPOSE: Vertical sleeve gastrectomy (VSG) improves metabolic health in young people with obesity but is accompanied by substantial loss of bone mass and estimated bone strength. We thus estimated fracture risk following VSG using the load-to-strength ratio (LSR), which integrates bone strength estimates with the predicted force of a fall. METHODS: Prospective 2-year study of youth ages 13-24 years with obesity undergoing VSG (n = 24) or lifestyle therapy (n = 34). We performed high-resolution peripheral quantitative computed tomography of the distal radius and microfinite element analysis to estimate bone strength and calculated LSR. RESULTS: VSG participants lost 26.4 ± 8.1% weight at year 1 (p < 0.001), which was sustained at year 2, while control participants gained weight at year 2 (4.5 ± 8.3%, p = 0.009). The predicted impact force decreased at years 1 and 2 following VSG (p < 0.001) but increased at year 2 among controls (p = 0.011). Estimated bone strength was unchanged at year 1 but decreased (p < 0.001) at year 2 following VSG, while bone strength did not change in controls. At year 1, the LSR decreased among VSG participants (p < 0.001), implying a lower risk of fracture. At year 2, the LSR was lower than baseline (p < 0.001), but higher compared to year 1 (p = 0.001). LSR did not change in the control group. CONCLUSIONS: Short-term estimated fracture risk at the radius following VSG decreases. However, ongoing bone loss despite stable weight between years 1 and 2 leads to a concerning rise in estimated fracture risk. Longer follow-up will be critical to evaluate the trajectory of fracture risk. (ClinicalTrials.gov NCT02557438, registered 9/23/2015).
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Fraturas Ósseas , Fraturas do Punho , Traumatismos do Punho , Humanos , Adolescente , Adulto Jovem , Estudos Prospectivos , Redução de Peso , Obesidade , GastrectomiaRESUMO
Osteocytes express parathyroid hormone (PTH)/PTH-related protein (PTHrP) receptors and respond to the PTHrP analog abaloparatide (ABL) and to the PTH 1-34 fragment teriparatide (TPTD), which are used to treat osteoporosis. Several studies indicate overlapping but distinct skeletal responses to ABL or TPTD, but their effects on cortical bone may differ. Little is known about their differential effects on osteocytes. We compared cortical osteocyte and skeletal responses to ABL and TPTD in sham-operated and ovariectomized mice. Administered 7 weeks after ovariectomy for 4 weeks at a dose of 40 µg/kg/d, TPTD and ABL had similar effects on trabecular bone, but ABL showed stronger effects in cortical bone. In cortical osteocytes, both treatments decreased lacunar area, reflecting altered peri-lacunar remodeling favoring matrix accumulation. Osteocyte RNA-Seq revealed that several genes and pathways were altered by ovariectomy and affected similarly by TPTD and ABL. Notwithstanding, several signaling pathways were uniquely regulated by ABL. Thus, in mice, TPTD and ABL induced a positive osteocyte peri-lacunar remodeling balance, but ABL induced stronger cortical responses and affected the osteocyte transcriptome differently. We concluded that ABL affected the cortical osteocyte transcriptome in a manner subtly different from TPTD, resulting in more beneficial remodeling/modeling changes and homeostasis of the cortex.
Assuntos
Proteína Relacionada ao Hormônio Paratireóideo , Teriparatida , Feminino , Camundongos , Animais , Teriparatida/farmacologia , Teriparatida/uso terapêutico , Proteína Relacionada ao Hormônio Paratireóideo/farmacologia , Proteína Relacionada ao Hormônio Paratireóideo/metabolismo , Osteócitos/metabolismo , Transcriptoma , Estrogênios/farmacologiaRESUMO
OBJECTIVE: To determine mechanisms contributing to impaired bone health in youth 24 months following sleeve gastrectomy (SG). DESIGN: Twenty-four-month longitudinal observational study. METHODS: Participants included 23 youth undergoing SG and 30 non-surgical controls (NS) 13-25 years old with moderate-to-severe obesity. Subjects underwent fasting labs for bone turnover markers (N-terminal propeptide of type 1 procollagen, C-telopeptide (CTX)), sex hormones, sex hormone binding globulin (SHBG), and enteric peptides, DXA for areal bone mineral density (aBMD) and body composition, high-resolution peripheral quantitative CT for volumetric BMD (vBMD) at the distal radius and tibia, and microfinite element analysis for strength estimates. RESULTS: Groups did not differ for mean age or BMI z-scores. Over 24 months, compared to NS, SG had greater reductions in BMI z-scores, and spine, hip, and femoral neck aBMD Z-scores (P ≤ .012), greater increases in serum CTX and SHBG (P ≤ .039), and greater decreases in estrone and ghrelin (P ≤ .021). Among females, estrone and free androgen index (FAI) decreased (P ≤ .022) in SG vs NS groups. After controlling for age and sex, decreases in BMI and lean mass were associated with decreases in total hip and femoral neck aBMD Z-scores, and decreases in radial total and trabecular vBMD and failure load, and tibial total and trabecular vBMD. Among females, after controlling for age, decreases in estrone were associated with decreases in spine aBMD Z-scores and radial total and trabecular vBMD, and decrease in FAI with decreases in radial failure load. CONCLUSION: Reductions in BMI, lean mass, and sex steroids over 24 months post-SG are associated with bone loss and could be targeted for preventative or therapeutic interventions. Clinical trial registration number: The study is registered in ClinicalTrials.gov (NCT02557438).
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Estrona , Coluna Vertebral , Feminino , Adolescente , Humanos , Adulto Jovem , Adulto , Densidade Óssea , Composição Corporal , GastrectomiaRESUMO
Background Sleeve gastrectomy (SG) is effective in the treatment of cardiometabolic complications of obesity but is associated with bone loss. Purpose To determine the long-term effects of SG on vertebral bone strength, density, and bone marrow adipose tissue (BMAT) in adolescents and young adults with obesity. Materials and Methods This 2-year prospective nonrandomized longitudinal study enrolled adolescents and young adults with obesity who underwent either SG (SG group) or dietary and exercise counseling without surgery (control group) at an academic medical center from 2015 to 2020. Participants underwent quantitative CT of the lumbar spine (L1 and L2 levels) to assess bone density and strength, proton MR spectroscopy to assess BMAT (L1 and L2 levels), and MRI of the abdomen and thigh to assess body composition. Student t and Wilcoxon signed-rank tests were used to compare 24-month changes between and within groups. Regression analysis was performed to evaluate associations between body composition, vertebral bone density, strength, and BMAT. Results A total of 25 participants underwent SG (mean age, 18 years ± 2 [SD], 20 female), and 29 underwent dietary and exercise counseling without surgery (mean age, 18 years ± 3, 21 female). Body mass index (BMI) decreased by a mean of 11.9 kg/m2 ± 5.21 [SD] after 24 months in the SG group (P < .001), while it increased in the control group (mean increase, 1.49 kg/m2 ± 3.10; P = .02). Mean bone strength of the lumbar spine decreased after surgery compared with that in control subjects (mean decrease, -728 N ± 691 vs -7.24 N ± 775; P < .001). BMAT of the lumbar spine increased after SG (mean lipid-to-water ratio increase, 0.10 ± 0.13; P = .001). Changes in vertebral density and strength correlated positively with changes in BMI and body composition (R = 0.34 to R = 0.65, P = .02 to P < .001) and inversely with vertebral BMAT (R = -0.33 to R = -0.47, P = .03 to P = .001). Conclusion SG in adolescents and young adults reduced vertebral bone strength and density and increased BMAT compared with those in control participants. Clinical trial registration no. NCT02557438 © RSNA, 2023 See also the editorial by Link and Schafer in this issue.
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Obesidade Infantil , Adolescente , Adulto Jovem , Feminino , Humanos , Estudos Longitudinais , Estudos Prospectivos , Gastrectomia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Espectroscopia de Prótons por Ressonância Magnética , Tomografia Computadorizada por Raios XRESUMO
Sleeve gastrectomy (SG) is effective in treating cardiometabolic complications of obesity but is associated with bone loss. Our aim was to determine the effect of SG on the lumbar spine by biomechanical CT analysis in adolescents/young adults with obesity. We hypothesized that SG would lead to a decrease in strength and bone mineral density (BMD) compared with nonsurgical controls. In a 12-month prospective nonrandomized study, adolescents/young adults with obesity underwent SG (n = 29, 18.0 ± 2.1 years, 23 female) or were followed without surgery (controls, n = 30, 17.95 ± 3.0 years, 22 female). At baseline and 12 months, participants underwent quantitative computed tomography (QCT) of L1 and L2 for biomechanical assessment and MRI of the abdomen and mid-thigh for body composition assessment. Twelve-month changes between groups and within groups were assessed. Analyses were controlled for baseline and 12-month changes in body mass index (BMI) by multivariable analyses. Regression analysis was performed to evaluate the effect of body composition on bone parameters. Our institutional review board (IRB) approved the study, and informed consent/assent was obtained. Participants in the SG group had a higher baseline BMI than controls (p = 0.01) and lost an average of 34.3 ± 13.6 kg 12 months after surgery, whereas weight was unchanged in controls (p < 0.001). There were significant reductions in abdominal adipose tissue and thigh muscle area in the SG group compared with controls (p < 0.001). Bone strength, bending stiffness, and average and trabecular volumetric BMD decreased in the SG group compared with controls (p < 0.001). After controlling for change in BMI, a 12-month reduction in cortical BMD was significant in the SG group compared with controls (p = 0.02). Reductions in strength and trabecular BMD were associated with reductions in BMI, visceral adipose tissue, and muscle (p ≤ 0.03). In conclusion, SG in adolescents decreased strength and volumetric BMD of the lumbar spine compared with nonsurgical controls. These changes were associated with decreases in visceral fat and muscle mass. © 2023 American Society for Bone and Mineral Research (ASBMR).
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Obesidade Infantil , Adolescente , Adulto Jovem , Humanos , Feminino , Estudos Longitudinais , Estudos Prospectivos , Densidade Óssea/fisiologia , Gastrectomia , Tomografia Computadorizada por Raios XRESUMO
Basic combat training (BCT) is a physically rigorous period at the beginning of a soldier's career that induces bone formation in the tibia. Race and sex are determinants of bone properties in young adults but their influences on changes in bone microarchitecture during BCT are unknown. The purpose of this work was to determine the influence of sex and race on changes in bone microarchitecture during BCT. Bone microarchitecture was assessed at the distal tibia via high-resolution peripheral quantitative computed tomography at the beginning and end of 8 weeks of BCT in a multiracial cohort of trainees (552 female, 1053 male; mean ± standard deviation [SD] age = 20.7 ± 3.7 years) of which 25.4% self-identified as black, 19.5% as race other than black or white (other races combined), and 55.1% as white. We used linear regression models to determine whether changes in bone microarchitecture due to BCT differed by race or sex, after adjusting for age, height, weight, physical activity, and tobacco use. We found that trabecular bone density (Tb.BMD), thickness (Tb.Th), and volume (Tb.BV/TV), as well as cortical BMD (Ct.BMD) and thickness (Ct.Th) increased following BCT in both sexes and across racial groups (+0.32% to +1.87%, all p < 0.01). Compared to males, females had greater increases in Tb.BMD (+1.87% versus +1.40%; p = 0.01) and Tb.Th (+0.87% versus +0.58%; p = 0.02), but smaller increases in Ct.BMD (+0.35% versus +0.61%; p < 0.01). Compared to black trainees, white trainees had greater increases in Tb.Th (+0.82% versus +0.61%; p = 0.03). Other races combined and white trainees had greater increases in Ct.BMD than black trainees (+0.56% and + 0.55% versus +0.32%; both p ≤ 0.01). Changes in distal tibial microarchitecture, consistent with adaptive bone formation, occur in trainees of all races and sexes, with modest differences by sex and race. Published 2023. This article is a U.S. Government work and is in the public domain in the USA. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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CONTEXT: Female athletes, particularly runners, with insufficient caloric intake for their energy expenditure [low energy availability (EA) or relative energy deficiency] are at risk for impaired skeletal integrity. Data are lacking in male runners. OBJECTIVE: To determine whether male runners at risk for energy deficit have impaired bone mineral density (BMD), microarchitecture, and estimated strength. DESIGN: Cross-sectional. SETTING: Clinical research center. PARTICIPANTS: 39 men (20 runners, 19 controls), ages 16-30 years. MAIN OUTCOME MEASURES: Areal BMD (dual-energy x-ray absorptiometry); tibia and radius volumetric BMD and microarchitecture (high-resolution peripheral quantitative computed tomography); failure load (microfinite element analysis); serum testosterone, estradiol, leptin; energy availability. RESULTS: Mean age (24.5 ± 3.8 y), lean mass, testosterone, and estradiol levels were similar; body mass index, percent fat mass, leptin, and lumbar spine BMD Z-score (-1.4 ± 0.8 vs -0.8 ± 0.8) lower (P < .05); and calcium intake and running mileage higher (P ≤ .01) in runners vs controls. Runners with EA Assuntos
Cálcio
, Leptina
, Humanos
, Masculino
, Feminino
, Estudos Transversais
, Densidade Óssea
, Absorciometria de Fóton
, Vértebras Lombares
, Testosterona
, Estradiol
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Gonadal hormones, such as testosterone and estradiol, modulate muscle size and strength in males and females. However, the influence of sex hormones on muscle strength in micro- and partial-gravity environments (e.g., the Moon or Mars) is not fully understood. The purpose of this study was to determine the influence of gonadectomy (castration/ovariectomy) on progression of muscle atrophy in both micro- and partial-gravity environments in male and female rats. Male and female Fischer rats (n = 120) underwent castration/ovariectomy (CAST/OVX) or sham surgery (SHAM) at 11 wk of age. After 2 wk of recovery, rats were exposed to hindlimb unloading (0 g), partial weight bearing at 40% of normal loading (0.4 g, Martian gravity), or normal loading (1.0 g) for 28 days. In males, CAST did not exacerbate body weight loss or other metrics of musculoskeletal health. In females, OVX animals tended to have greater body weight loss and greater gastrocnemius loss. Within 7 days of exposure to either microgravity or partial gravity, females had detectable changes to estrous cycle, with greater time spent in low-estradiol phases diestrus and metestrus (â¼47% in 1 g vs. 58% in 0 g and 72% in 0.4 g animals, P = 0.005). We conclude that in males testosterone deficiency at the initiation of unloading has little effect on the trajectory of muscle loss. In females, initial low estradiol status may result in greater musculoskeletal losses.NEW & NOTEWORTHY We find that removal of gonadal hormones does not exacerbate muscle loss in males or females during exposure to either simulated microgravity or partial-gravity environments. However, simulated micro- and partial gravity did affect females' estrous cycles, with more time spent in low-estrogen phases. Our findings provide important data on the influence of gonadal hormones on the trajectory of muscle loss during unloading and will help inform NASA for future crewed missions to space and other planets.
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Meio Ambiente Extraterreno , Marte , Humanos , Ratos , Masculino , Feminino , Animais , Ovariectomia , Testosterona/fisiologia , Estradiol , Músculo Esquelético , Orquiectomia , Hormônios Gonadais , Ratos Endogâmicos F344 , Redução de PesoRESUMO
CONTEXT: Vertical sleeve gastrectomy (VSG) is an increasingly common tool to achieve weight loss and improve metabolic health in adolescents and young adults with obesity, although it may adversely affect bone health. OBJECTIVE: This work aimed to evaluate the effect of VSG on bone health in youth. METHODS: An observational 2-year study was conducted at a tertiary care center of 66 patients aged 13 to 24 years with moderate-to-severe obesity meeting criteria for VSG. The patients underwent VSG (n = 30) or nonsurgical (n = 36) management per the decision of patient and clinical team. Main outcome measures included dual-energy x-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HRpQCT) measures of bone mineral density (BMD), geometry, and microarchitecture. RESULTS: VSG patients achieved 25.3 ± 2.0% weight loss at 2 years (P < .001) while control subjects gained 4.0 ± 2.0% (P = .026). Total hip BMD declined 8.5 ± 1.0% following VSG compared with 0.1 ± 1.0% gain in controls (P < .001), with similar results at the femoral neck (P < .001). Total volumetric BMD (vBMD) decreased both at the distal radius and tibia following VSG (P < .001) driven primarily by trabecular vBMD loss (P < .001). Two-year changes in cortical vBMD did not differ between groups, though cortical porosity decreased following VSG both at the radius and tibia (P = .048 and P < .001). Cortical thickness increased in controls but not in VSG (P = .022 and P = .002 for between-group comparisons at the radius and tibia, respectively). Following VSG, estimated failure load decreased at the radius and did not demonstrate the physiologic increases at the tibia observed in controls. CONCLUSION: VSG leads to progressive changes in bone health over 2 years, and may lead to increased skeletal fragility in adolescents and young adults.
Assuntos
Densidade Óssea , Osso e Ossos , Humanos , Adolescente , Adulto Jovem , Estudos Longitudinais , Densidade Óssea/fisiologia , Absorciometria de Fóton , Obesidade , Rádio (Anatomia)/diagnóstico por imagem , Rádio (Anatomia)/fisiologia , Tíbia/diagnóstico por imagem , Tíbia/fisiologiaRESUMO
BACKGROUND: Peptide YY (PYY) is an anorexigenic gut hormone that also has anti-osteogenic effects, inhibiting osteoblastic activity and inducing catabolic effects. It has been postulated that increases in PYY after Roux-en-Y gastric bypass (RYGB) contribute to declines in bone mineral density (BMD) and increases in bone turnover. The aim of this study is to determine the role of the PYY Y2-receptor in mediating bone loss post-RYGB in mice. METHODS: We compared adult male wildtype (WT) and PYY Y2 receptor-deficient (KO) C57BL/6 mice that received RYGB (WT: n = 8; KO: n = 9), with sham-operated mice (Sham; WT: n = 9; KO: n = 10) and mice that were food-restricted to match the weights of the RYGB-treated group (Weight-Matched, WM; WT: n = 7; KO: n = 5). RYGB or sham surgery was performed at 15-16 weeks of age, and mice sacrificed 21 weeks later. We characterized bone microarchitecture with micro-computed tomography (µCT) at the distal femur (trabecular) and femoral midshaft (cortical). Differences in body weight, bone microarchitecture and biochemical bone markers (parathyroid hormone, PTH; C-telopeptide, CTX; and type 1 procollagen, P1NP) were compared using 2-factor ANOVA with Tukey's adjustments for multiple comparisons. RESULTS: Body weights were similar in the WT-RYGB, WT-WM, KO-RYGB, and KO-WM: 41-44 g; these groups weighed significantly less than the Sham surgery groups: 55-57 g. Trabecular BMD was 31-43 % lower in RYGB mice than either Sham or WM in WT and KO groups. This deficiency in trabecular bone was accompanied by a lower trabecular number (19 %-23 %), thickness (22 %-30 %) and increased trabecular spacing (25 %-34 %) in WT and KO groups (p < 0.001 for all comparisons vs. RYGB). RYGB led to lower cortical thickness, cortical tissue mineral density, and cortical bone area fraction as compared to Sham and WM in WT and KO groups (p ≤ 0.004 for all). There were no interactions between genotype and bone microarchitecture, with patterns of response to RYGB similar in both WT and KO groups. CTX and P1NP were significantly higher in RYGB mice than WM in WT and KO groups. PTH did not differ among groups. CONCLUSIONS: RYGB induced greater trabecular and cortical deficits and high bone turnover than observed in weight-matched mice, with a similar pattern in the WT and Y2RKO mice. Thus, skeletal effects of RYGB are independent of weight loss, and furthermore, PYY signaling through Y2R is not a key mediator of bone loss post-RYGB.
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Doenças Ósseas Metabólicas , Derivação Gástrica , Animais , Masculino , Camundongos , Densidade Óssea/fisiologia , Camundongos Endogâmicos C57BL , Peptídeo YY , Microtomografia por Raio-XRESUMO
The 22nd Annual Santa Fe Bone Symposium (SFBS) was a hybrid meeting held August 5-6, 2022, with in-person and virtual attendees. Altogether, over 400 individuals registered, a majority of whom attended in-person, representing many states in the USA plus 7 other countries. The SFBS included 10 plenary presentations, 2 faculty panel discussions, satellite symposia, Bone Health & Osteoporosis Foundation Fracture Liaison Service Boot Camp, and a Project ECHO workshop, with lively interactive discussions for all events. Topics of interest included fracture prevention at different stages of life; how to treat and when to change therapy; skeletal health in cancer patients; advanced imaging to assess bone strength; the state of healthcare in the USA; osteosarcopenia; vitamin D update; perioperative bone health care; new guidelines for managing primary hyperparathyroidism; new concepts on bone modeling and remodeling; and an overview on the care of rare bone diseases, including hypophosphatasia, X-linked hypophosphatemia, tumor induced osteomalacia, osteogenesis imperfecta, fibrodysplasia ossificans progressiva, and osteopetrosis. The SFBS was preceded by the Santa Fe Fellows Workshop on Osteoporosis and Metabolic Bone Diseases, a collaboration of the Endocrine Fellows Foundation and the Osteoporosis Foundation of New Mexico. From the Workshop, 4 participating fellows were selected to give oral presentations at the bone symposium. These proceedings represent the clinical highlights of 2022 SFBS presentations and the discussions that followed, all with the aim of optimizing skeletal health and minimizing the consequences of fragile bones.
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Doenças Ósseas Metabólicas , Osteoporose , Fraturas por Osteoporose , Humanos , Absorciometria de Fóton , Osteoporose/tratamento farmacológico , Doenças Ósseas Metabólicas/terapia , Fraturas por Osteoporose/prevenção & controleRESUMO
Glucocorticoid excess suppresses osteocyte remodeling of surrounding bone minerals, causes apoptosis of osteoblasts and osteocytes, and disrupts bone remodeling, eventually, leading to glucocorticoid-induced osteoporosis and bone fragility. Preventing apoptosis and preserving osteocyte morphology could be an effective means of preventing bone loss during glucocorticoid treatment. We hypothesized that osteocrin, which preserves osteocyte viability and morphology in Sp7-deficient mice, could prevent osteocyte death and dysfunction in a glucocorticoid excess model. We used adeno-associated virus (AAV8) to induce osteocrin overexpression in mice one week before implantation with prednisolone or placebo pellets. After 28 days, prednisolone caused the expected reduction in cortical bone thickness and osteocyte canalicular length in control AAV8-treated mice, and these effects were blunted in mice receiving AAV8-osteocrin. Glucocorticoid-induced changes in cortical porosity, trabecular bone mass, and gene expression were not prevented by osteocrin. These findings support a modest therapeutic potential for AAV8-osteocrin in preserving osteocyte morphology during disease.
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Type 2 diabetes (T2D) is associated with increased risk of fractures. However, it is unclear whether current osteoporosis treatments reduce fractures in individuals with diabetes. The aim of the study was to determine whether presence of T2D influences the efficacy of antiresorptive treatment for osteoporosis using the Foundation for the National Institutes of Health (FNIH)-American Society for Bone and Mineral Research (ASBMR)-Study to Advance Bone Mineral Density (BMD) as a Regulatory Endpoint (SABRE) cohort, which includes individual patient data from randomized trials of osteoporosis therapies. In this study we included 96,385 subjects, 6.8% of whom had T2D, from nine bisphosphonate trials, two selective estrogen receptor modulator (SERM) trials, two trials of menopausal hormone therapy, one denosumab trial, and one odanacatib trial. We used Cox regression to obtain the treatment hazard ratio (HR) for incident nonvertebral, hip, and all fractures and logistic regression to obtain the treatment odds ratio (OR) for incident morphometric vertebral fractures, separately for T2D and non-DM. We used linear regression to estimate the effect of treatment on 2-year change in BMD (n = 49,099) and 3-month to 12-month change in bone turnover markers (n = 12,701) by diabetes status. In all analyses, we assessed the interaction between treatment and diabetes status. In pooled analyses of all 15 trials, we found that diabetes did not impact treatment efficacy, with similar reductions in vertebral, nonvertebral, all, and hip fractures, increases in total hip and femoral neck BMD, and reductions in serum C-terminal cross-linking telopeptide (CTX), urinary N-telopeptide of type I collagen/creatinine (NTX/Cr) and procollagen type 1 N propeptide (P1NP) (all interactions p > 0.05). We found similar results for the pooled analysis of bisphosphonate trials. However, when we considered trials individually, we found a few interactions within individual studies between diabetes status and the effects of denosumab and odanacatib on fracture risk, change in BMD or bone turnover markers (BTMs). In sum, these results provide strong evidence that bisphosphonates and most licensed antiresorptive drugs are effective at reducing fracture risk and increasing BMD irrespective of diabetes status. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Assuntos
Conservadores da Densidade Óssea , Diabetes Mellitus Tipo 2 , Fraturas do Quadril , Osteoporose , Humanos , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Denosumab/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Difosfonatos/uso terapêutico , Fraturas do Quadril/tratamento farmacológico , Osteoporose/tratamento farmacológicoRESUMO
STUDY DESIGN: Prospective randomized placebo controlled animal trial. OBJECTIVE: Determine the effect of daily subcutaneous abaloparatide injection on the intervertebral fusion rate in rabbits undergoing posterolateral fusion. STUDY OF BACKGROUND DATA: Despite the wide utilization of spine fusion, pseudarthrosis remains prevalent, and results in increased morbidity. Abaloparatide is a novel analog of parathyroid hormone-related peptide (1-34) and has shown efficacy in a rat posterolateral spine fusion model to increase fusion rates. The effect of abaloparatide on the fusion rate in a larger animal model remains unknown. MATERIALS AND METHODS: A total of 24 skeletally mature New Zealand White male rabbits underwent bilateral posterolateral spine fusion. Following surgery, the rabbits were randomized to receive either saline as control or abaloparatide subcutaneous injection daily. Specimens underwent manual assessment of fusion, radiographic analysis with both x-ray and high-resolution peripheral quantitative computed tomography, and biomechanical assessment. RESULTS: Rabbits that received abaloparatide had a 100% (10/10) fusion rate compared with 45% (5/11) for controls ( P <0.02) as assessed by manual palpation. Radiographic analysis determined an overall mean fusion score of 4.17±1.03 in the abaloparatide group versus 3.39±1.21 for controls ( P <0.001). The abaloparatide group also had a greater volume of bone formed with a bone volume of 1209±543 mm 3 compared with 551±152 mm 3 ( P <0.001) for controls. The abaloparatide group had significantly greater trabecular bone volume fraction and trabecular thickness and lower specific bone surface and connectivity density in the adjacent levels when compared with controls. Abaloparatide treatment did not impact trabecular number or separation. There were no differences in biomechanical testing in flexion, extension, or lateral bending ( P >0.05) between groups. CONCLUSIONS: Abaloparatide significantly increased the fusion rate in a rabbit posterolateral fusion model as assessed by manual palpation. In addition, there were marked increases in the radiographic evaluation of fusion.
Assuntos
Proteína Relacionada ao Hormônio Paratireóideo , Fusão Vertebral , Animais , Masculino , Coelhos , Ratos , Transplante Ósseo/métodos , Vértebras Lombares/cirurgia , Osteogênese , Proteína Relacionada ao Hormônio Paratireóideo/farmacologia , Proteína Relacionada ao Hormônio Paratireóideo/uso terapêutico , Estudos Prospectivos , Fusão Vertebral/métodosRESUMO
CONTEXT: Sleeve gastrectomy (SG) improves metabolic endpoints but is associated with impaired bone outcomes. OBJECTIVE: To determine mechanisms contributing to impaired bone health in youth following SG. METHODS: 12-month longitudinal observational study in a multidisciplinary tertiary-care hospital, including 64 youth 13-25 years old with moderate-to-severe obesity (51 females); 30 underwent SG and 34 were nonsurgical (NS) controls. SG was undertaken after a combined decision-making process between treatment team and patient. The main outcome measures were fasting blood for enteric peptides, sex steroids, sclerostin, and bone turnover markers (N-terminal propeptide of type 1 procollagen [P1NP] and C-terminal cross-linking telopeptide [CTX]); dual-energy X-ray absorptiometry measures of areal bone mineral density (aBMD) and body composition; high resolution peripheral quantitative computed tomography; measures of volumetric BMD (vBMD); microfinite element analysis of strength estimates (distal radius and tibia). RESULTS: SG had greater reductions in body mass index (BMI) z-scores, serum estrone, and the free androgen index (FAI) (Pâ ≤â .046), and greater increases in sclerostin, P1NP, and CTX (Pâ ≤â .010) than NS controls. Fasting ghrelin decreased in SG vs NS (Pâ <â .0001); fasting peptide YY did not change. Most changes were driven by female SG participants. Among females (the majority of study participants), after controlling for baseline age and race, reductions in total hip aBMD Z-scores were positively associated with changes in BMI, lean mass, estrone, FAI, and ghrelin, and inversely with changes in sclerostin.. Decreases in total vBMD of the radius and tibia were associated positively with decreases in BMI. Increases in CTX were associated with decreases in BMI, lean mass, and ghrelin, and increases in sclerostin. CONCLUSION: Bone loss after SG in youth is associated with changes in body composition, sex steroids, sclerostin, and enteric peptides. These are potential targets for future preventative or therapeutic strategies.
Assuntos
Estrona , Grelina , Absorciometria de Fóton , Proteínas Adaptadoras de Transdução de Sinal , Adolescente , Adulto , Densidade Óssea , Osso e Ossos , Feminino , Gastrectomia , Humanos , Masculino , Adulto JovemRESUMO
Bone stress injuries, including stress fractures, are overuse injuries that lead to substantial morbidity in active individuals. These injuries occur when excessive repetitive loads are introduced to a generally normal skeleton. Although the precise mechanisms for bone stress injuries are not completely understood, the prevailing theory is that an imbalance in bone metabolism favours microdamage accumulation over its removal and replacement with new bone via targeted remodelling. Diagnosis is achieved by a combination of patient history and physical examination, with imaging used for confirmation. Management of bone stress injuries is guided by their location and consequent risk of healing complications. Bone stress injuries at low-risk sites typically heal with activity modification followed by progressive loading and return to activity. Additional treatment approaches include non-weight-bearing immobilization, medications or surgery, but these approaches are usually limited to managing bone stress injuries that occur at high-risk sites. A comprehensive strategy that integrates anatomical, biomechanical and biological risk factors has the potential to improve the understanding of these injuries and aid in their prevention and management.
Assuntos
Fraturas de Estresse , Osso e Ossos , Fraturas de Estresse/diagnóstico , Fraturas de Estresse/etiologia , Fraturas de Estresse/terapia , HumanosRESUMO
BACKGROUND: Bariatric surgery has been shown to result in weight loss, improved hemoglobin A1C, and decreased mortality but can also lead to bone loss and increased fracture rates. Serum IGFBP-2 is elevated in patients after bariatric surgery and although it may lead to improved blood glucose, may also drive bone resorption, and inhibit IGF-I action. This study tested the hypothesis that Igfbp2-/- mice were acutely protected from bone loss after vertical sleeve gastrectomy (VSG). METHODS: Thirty-four mice, 17 Igfbp2-/- and 17 + / + underwent a hand-sewn VSG or sham surgery, at 16 weeks of age. Mice were harvested at 20 weeks of age. DXA was measured for body composition, areal bone mineral density (aBMD), areal bone mineral content (aBMC), femoral bone mineral density (fBMD), and femoral bone mineral content (fBMC) at 15, 18, and 20 weeks of age. Micro-computed tomography and serum ELISA assays were measured and analyzed at 20 weeks of age. RESULTS: Both Igfbp2-/- and + / + mice lost significant weight (P = 0.0251, P = 0.0003, respectively) and total fat mass (P = 0.0082, P = 0.0004, respectively) at 4 weeks after VSG. Igfbp2+/+ mice lost significant aBMD, fBMD, fBMC, trabecular BMD, trabecular BV/TV and cortical tissue mineral density (P = 0.0150, P = 0.0313, P = 0.0190, P = 0.0072, and 0.0320 respectively). The Igfbp2-/- mice did not show significant bone loss in these parameters nor in trabecular BV/TV. Both Igfbp2-/- and + / + mice had less cortical bone area (P = 0.0181, P = < .00001), cortical area over total area (P = 0.0085, P = 0.0007), and cortical thickness (P = 0.0050, P = < 0.0001), respectively. Igfbp2+/+ mice demonstrated significantly lower polar, minimum, and maximum moments of inertia (P = 0.0031, P = 0.0239, and P = 0.0037, respectively). Igfbp2+/+ had significantly higher levels of IGFBP-2 at 2 weeks postoperatively after VSG (P = 0.035), and elevated levels of CTx and P1NP (P = 0.0127, P = 0.0058, respectively). CONCLUSIONS: Igfbp2-/- mice were protected against trabecular bone loss and had attenuated cortical bone loss 4 weeks after VSG.
Assuntos
Osso Esponjoso , Gastrectomia/efeitos adversos , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina , Osteoporose/genética , Animais , Densidade Óssea , Osso Esponjoso/diagnóstico por imagem , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Camundongos , Osteoporose/patologia , Microtomografia por Raio-XRESUMO
BACKGROUND: Fractures secondary to osteoporosis, particularly those of the hip and spine, are a major public health concern with high social and economic costs. The Local Osteo-Enhancement Procedure (LOEP) is an approach intended to strengthen skeletal areas that are at the highest risk for fracture due to osteoporosis. LOEP involves the implantation of AGN1, a triphasic, calcium-based, osteoconductive material which is then resorbed and replaced by bone. Since alendronate is the most prescribed osteoporotic treatment, the purpose of this canine study is to determine if the newly formed bone has the same properties as normal bone and whether alendronate treatment impacts AGN1 resorption and replacement with bone. METHODS: Sixty skeletally mature male hounds (24-38 kg) were evenly divided between alendronate (0.2 mg/kg/day) and non-alendronate treatment groups. A critical-size core bone defect created in one proximal humerus was implanted with AGN1 while the contralateral non-operated humerus served as a paired control in each animal. Animals were sacrificed 13, 26, and 52 weeks post-operatively (10 per treatment per timepoint). The control and treatment site bone specimens from each animal were examined using radiographic, histomorphometric, and biomechanical techniques. Results between alendronate-treated and non-alendronate-treated animals were compared as groups. RESULTS: AGN1 implant material was consistently resorbed and replaced by bone in all animals. At 52 weeks, only minimal residual implant material could be detected (0.9 ± 2.3% non-alendronate group; 2.2 ± 3.1% alendronate group), and new bone filled the defects in both the non-alendronate and alendronate groups. At 13 and 26 weeks, microCT revealed the newly formed bone in the defects had significantly higher trabecular bone volume and number connectivity than control bone in both groups. Mechanical testing demonstrated that the new bone had ultimate compressive strength and modulus equivalent to control bone as early as 13 weeks post-surgery which was maintained to 52 weeks in both groups. CONCLUSIONS: In this canine critical-sized humeral core defect model, AGN1 was progressively replaced by normal bone as evaluated by all outcome measures. Concurrent alendronate therapy did not significantly impact AGN1 resorption or new bone formation. These results demonstrate that AGN1 can be used in conjunction with alendronate in non-osteoporotic animals. CLINICAL RELEVANCE: This study suggests that the AGN1 implant material demonstrates potential for local restoration of bone in critical-size core defects, and that the material is compatible with alendronate drug therapy. Further studies will be required to determine if these results apply to other osteoporosis medications.