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1.
Arch Orthop Trauma Surg ; 139(1): 53-59, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30328508

RESUMEN

Staged treatment for severe lower extremity fractures is coming into widespread use, and some reports have described internal fixation (IF) using a temporary external fixator for primary care as an intraoperative retention tool. However, the infection risk with this procedure has not been examined sufficiently. To our knowledge, this article is the first report focusing exclusively on this specific surgical technique. A key point of our developed protocol for internal plate fixation with this technique to avoid postoperative infection is a precisely structured sterilization procedure, which required multiple changes of sterile surgical gloves. In all 19 fractures treated with our set protocol, postoperative infection did not occur. In this regard, however, a goal of definitive IF at the time of initial treatment is essential for this specific procedure. This technique could help orthopaedic trauma surgeons to import a temporary external fixator into the operative field for definitive IF, with less concern regarding risk of infection.


Asunto(s)
Placas Óseas , Fijadores Externos , Fijación Interna de Fracturas , Fracturas Óseas/cirugía , Traumatismos de la Pierna/cirugía , Estudios de Cohortes , Fijación Interna de Fracturas/efectos adversos , Fijación Interna de Fracturas/instrumentación , Fijación Interna de Fracturas/métodos , Humanos , Infección de la Herida Quirúrgica
2.
J Orthop Sci ; 19(4): 579-86, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24789301

RESUMEN

BACKGROUND: We have studied stress fractures of the bowed femoral shaft (SBFs) among elderly Japanese for over a decade. On the other hand, severely suppressed bone turnover (SSBT) after long-term bisphosphonates (BPs) use has been considered to be one of the causes of low-energy diaphyseal femoral fractures, often called atypical femoral fractures (AFFs). Some studies have shown that BPs use for more than 5 years is associated with an increased risk of AFFs. Here, we present a report of our SBF case series experienced in the past 15 years in order to examine whether bowing deformity should be considered among the causes of AFFs. METHODS: Subjects were 13 Japanese female patients with low-energy femoral shaft fractures. Mean age at injury was 77.0 years (range 67-88 years). All patients met the criteria of the AFFs' case definition. The first author treated 11 of the 13 patients over 8 years (2005-2012) based on the concept of SBFs. Regarding the regional characteristics of these patients, 10 were treated at 2 rural hospitals, and 3 were treated at 3 urban hospitals. Retrospectively, we assessed fracture type and location, existence of fracture on the contralateral side, bowing deformity, and duration of BPs use. RESULTS: All 13 cases were AO/OTA type 32-A. Incomplete or previous fracture on the contralateral side was noted in 10 cases. Obvious bowing deformity of the femoral shaft was noted in 12 cases. BPs were taken in 7 cases, only 3 of which involved BPs use for more than 5 years. CONCLUSIONS: We experienced 12 cases of low-energy femoral shaft fractures associated with bowing deformity. Six cases were not treated with BPs at all. Stress fractures associated with a femoral shaft bowing deformity do actually exist and should be recognized as another cause of AFFs.


Asunto(s)
Fracturas del Fémur/etiología , Fémur/anomalías , Fracturas por Estrés/etiología , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Femenino , Humanos , Estudios Retrospectivos
3.
Injury ; : 111136, 2023 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-37867026

RESUMEN

INTRODUCTION: Although the diagnostic criteria for atypical femoral fracture (AFF) exclude periprosthetic fractures, reports of periprosthetic femoral fractures with characteristics of AFF are rapidly increasing. In this study, we investigated the frequency and pathogenesis of periprosthetic AFF associated with total knee arthroplasty (TKA) based on a theory of AFF subtypes that divides AFFs into two main types: fragility stress fractures of the bowed femoral shaft in the mid-shaft and "typical" subtrochanteric AFFs due to suppression of bone turnover (e.g., by bisphosphonates). PATIENTS AND METHODS: This multicenter prospective study of AFFs was conducted from 2015 through 2022. Clinical, pathological, and morphological characteristics were investigated in patients with periprosthetic AFFs associated only with non-stem TKA. Then, biomechanical investigation of the periprosthetic AFF was performed by computer tomography-based finite element analysis (CT/FEA) using two models with different load axes to examine how the correction of lower limb alignment by TKA influences the tensile stress distribution of the femur and the location of the AFF. RESULTS: Four of 61 AFFs (6.6%) were identified to be periprosthetic AFF (1 mid-shaft; 3 subtrochanteric). Periprosthetic AFFs had characteristics including mechanical stress due to bowing deformity and potentially suppressed bone turnover due to long-term exposure to specific drugs (e.g., bisphosphonates and glucocorticoids). Although 2 periprosthetic AFFs appeared to involve a bowed femur, one with both of the aforementioned characteristics occurred in the subtrochanteric region, which would be an unusual site for a bowed AFF, and it was demonstrated histologically to have biological activity at the fracture site, suggesting a stress fracture. Furthermore, CT/FEA revealed that tensile stress distribution changed proximally as load axis was shifted laterally according to correction of lower limb alignment by TKA. CONCLUSION: Orthopedic surgeons should recognize the presence of TKA-associated periprosthetic AFF caused by various factors including specific drugs, bowing deformity, and lower limb alignment. X-rays of the full-length femurs should be checked regularly after TKA, especially in patients with bowed femurs or long-term exposure to specific drugs.

4.
JBMR Plus ; 7(7): e10749, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37457876

RESUMEN

Patients on bone-modifying agents (BMAs) for bone metastases are at risk of atypical femoral fractures (AFFs), which can lead to a sudden deterioration in performance status. In this study, we sought to determine the prevalence of radiographic precursory signs of AFF in patients on oncologic BMAs. Forty-two patients (23 men, 19 women; mean age 68.8 ± 10.0 years) on oncologic BMAs (zoledronate for >3 years and/or denosumab for >1 year) and without clinical symptoms were enrolled between 2019 and 2021. All patients were receiving denosumab at enrollment and 5 had previously used zoledronate. The mean duration of BMA use was 31.2 ± 18.5 months. Radiographs of both femurs were screened for precursory signs of AFF (e.g., thickening of the lateral cortex). The patients were divided into two groups according to thickening status and compared by duration of BMA use. They were also divided into three groups by duration of BMA use (12-23 months, n = 18; 24-59 months, n = 19; ≥60 months, n = 5), and the prevalence of apparent thickenings was examined. As a result, 18 patients (42.9%) showed minute local or diffuse thickening and 10 (23.8%) showed apparent local thickening. The duration of BMA use was significantly longer in patients with apparent thickening than in those without (47.3 ± 23.6 months [n = 10] versus 26.2 ± 13.5 months [n = 32]; p < 0.05). The prevalence of apparent thickening increased with increasing duration of BMA use (12-23 months, 5.6%; 24-59 months, 31.6%; ≥60 months, 60.0%). In conclusion, radiographic precursory signs of AFF are common in patients on oncologic BMAs. Radiographic screening for AFF could be relevant in patients who have been on long-term oncologic BMAs, even if asymptomatic. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

5.
Spine Surg Relat Res ; 6(3): 294-302, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35800622

RESUMEN

Introduction: Breast cancer is one of the most frequent primary tumors that cause spinal metastases. Metastasis consequences impair both the patient's overall prognosis and quality of life. We previously developed a porous hydroxyapatite collagen composite (HAp/Col) as an osteoconductive scaffold. HAp/Col is a commercially available artificial bone that is frequently utilized in spinal fusion. Because of its high absorbance capacity, HAp/Col is regarded as a good chemical carrier. Methods: This study investigated the effect of local administration of paclitaxel combined with HAp/Col scaffold on breast cancer metastasis. High-performance liquid chromatography was used to assess the in vitro release of paclitaxel from HAp/Col. In an in vivo rat model, the inhibitory effects of paclitaxel-impregnated scaffolds on local osteogenesis was examined, and then the local suppression effects on metastatic cancer were investigated. Results: In vitro testing revealed that roughly 30% of the paclitaxel was released within 96 hours. Paclitaxel-impregnated HAp/Col inhibited local osteogenesis for the first 8 weeks in a rat femur. However, at 12 weeks following surgery, this negative effect appeared to have subsided. In the metastatic model, all rats in the control group reached the humane endpoint 14 days after surgery. On the other hand, the average time to the endpoint in the paclitaxel group was 26.5 days, which was substantially longer than that in the control group. Long-term survivors treated with paclitaxel had no remaining tumor cells in the femoral bone, and osteogenesis was seen surrounding the HAp/Col. Conclusions: Paclitaxel-impregnated HAp/Col reduced local tumor development and extended the time to the target endpoint in rats with metastases from breast cancer. This study shows that local implantation of paclitaxel-impregnated HAp/Col may be a viable therapeutic option for the management of breast cancer metastases.

6.
Ther Adv Endocrinol Metab ; 12: 20420188211049619, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34671453

RESUMEN

Stress fractures have traditionally been classified into three categories: fatigue fractures due to overuse of bone with normal elastic resistance; insufficiency fractures due to everyday physiological stress on fragile bone with poor elastic resistance; and pathologic fractures due to bone weakness involving tumors. The concept of atypical fractures has emerged and is considered a type of stress fracture. However, there has been some inconsistency in interpretation when using the traditional classification of stress fractures, and atypical femoral fractures (AFFs) can potentially be classified into subtypes: "typical" AFFs involving bone turnover suppression due to specific drugs (e.g. bisphosphonates) and fragility fractures of the bowed femoral shaft. In this article, the classification of stress fractures is redefined with the addition of atypical fractures as a fourth category, in which biological activity for fracture healing is absent, to promote consistent understanding and interpretation of clinical conditions involving stress fractures.

7.
J Bone Oncol ; 23: 100301, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32642421

RESUMEN

BACKGROUND: As the life expectancy of cancer-bearing patients has increased, more patients with bone metastasis are receiving long-term treatment with bone-modifying agents (BMAs; e.g., zoledronate and denosumab), which are a risk factor for developing atypical femoral fracture (AFF). In this study, we surveyed the risk of iatrogenic AFF using a clinical database on treatment of bone metastasis in the past 10 years. METHODS: From April 2011 through October 2019, 721 patients with bone metastasis (436 men, 285 women; mean age, 65.7 ± 12.4 years) were registered under the bone metastasis consultation system, which has been run by orthopaedic surgeons since 2011, at a university hospital in Japan. We retrospectively reviewed the database to identify patients who had received BMAs for treatment of bone metastasis, and we investigated the incidence of critical skeletal-related events (including AFF) which required surgical interventions by orthopaedic surgeons. RESULTS: BMAs were administered to 529 patients (73.4%). Orthopaedic surgery for the treatment of skeletal-related events was performed in 36 patients (5.0%): femur, 13 (1.8%); others, 23 (3.2%). Eight AFFs in 5 patients (breast cancer, n = 4; prostate cancer, n = 1), who all had prior exposure to zoledronate or denosumab before onset of AFF, were treated with internal fixation using intramedullary nailing. In 192 patients with no BMA exposure, critical (surgically treated) AFF was not detected. In summary, the incidence of critical AFF was 0.9% among 529 patients who received BMAs for treatment of bone metastasis, and the incidence was 6.6% when limited to breast cancer patients (4 of 61). CONCLUSION: In treatment of bone metastasis using BMAs, especially for breast cancer patients, attention should be paid to the risk of developing AFFs. Routine radiographic screening for AFF might be necessary in patients with prolonged BMA use for bone metastasis, even if asymptomatic. This report alerts all physicians and surgeons involved in the management of cancer patients, especially those with bone metastasis, regarding the risk of AFF following BMA use.

8.
Bone ; 137: 115453, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32470545

RESUMEN

BACKGROUND: We have investigated mid-shaft stress fractures of the bowed femoral shaft (SBFs), well before the first report of an association between suppression of bone turnover and atypical femoral fractures (AFFs). Although all cases of SBF meet the criteria for AFF, SBFs can also occur in patients with no exposure to bone turnover suppression-related drugs (e.g., bisphosphonates). Using bone morphometry and biomechanical analyses, we devised a theory of AFF subtypes, dividing AFFs into fragility SBFs in the mid-shaft and "typical" subtrochanteric AFFs caused by suppressed bone turnover. The aim of this multicenter prospective study was to provide evidence for this novel concept in terms of biological activity. METHODS: The study was conducted at 12 hospitals in Japan from 2015 through 2019. Thirty-seven elderly women with AFF were included and classified according to location of the fracture into a mid-shaft AFF group (n = 18) and a subtrochanteric AFF group (n = 19). Patient demographics and clinical characteristics were investigated to compare the two groups. The main focus was on histological analysis of the fracture site, and bone metabolism markers were evaluated to specifically estimate biological activity. RESULTS: All patients in the subtrochanteric AFF group had a history of long-term (>3 years) exposure to specific drugs that have been reported to cause AFF, but 5 of the 18 patients in the mid-shaft AFF group had no history of exposure to such drugs. Femoral bowing was significantly greater in the mid-shaft AFF group (p < 0.001). In the histological analysis, active bone remodeling or endochondral ossification was observed in the mid-shaft AFF group, whereas no fracture repair-related biological activity was observed in the majority of patients in the subtrochanteric AFF group. Levels of tartrate-resistant acid phosphatase-5b and undercaroxylated osteocalcin were significantly lower in the subtrochanteric AFF group (p < 0.05). CONCLUSION: The possibility of our devised AFF subtype theory was demonstrated. Biological activity tends not to be suppressed in mid-shaft SBFs unlike in "typical" subtrochanteric AFFs involving bone turnover suppression. Although validation of the proposed theory in other populations is needed, we suggest that the pathology and treatment of AFFs be reconsidered based on its subtype.


Asunto(s)
Conservadores de la Densidad Ósea , Fracturas del Fémur , Fracturas por Estrés , Anciano , Difosfonatos , Femenino , Fracturas del Fémur/diagnóstico por imagen , Fracturas por Estrés/diagnóstico por imagen , Humanos , Japón , Estudios Prospectivos
9.
J Clin Med ; 9(10)2020 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-33023020

RESUMEN

Previous studies have shown better clinical outcomes after total hip arthroplasty (THA) compared to hemiarthroplasty (HA) for displaced femoral neck fracture. However, few studies have focused on the surgical risks of the two procedures. Therefore, we investigated the perioperative complications of HA and THA in femoral neck fracture, using a large nationwide inpatient database. A total of 286,269 patients (281,140 patients with HA and 5129 with THA) with a mean age of 81.7 were enrolled and HA and THA patients were matched by a propensity score to adjust for patient and hospital characteristics. Patients in a matched cohort were analyzed to compare complications and mortality. The systemic complication rate was not significantly different after a propensity score matching of 4967 pairs of patients. However, the incidence of both hip dislocation and revision surgery was more frequent in the THA group (Risk difference (RD), 2.74; 95%Confidence interval(CI), 2.21-3.27; p < 0.001; RD, 2.82; 95%CI, 2.27-3.37; p < 0.001, respectively). There was no significant difference in 30 day in-hospital mortality among the two groups. The risk of dislocation and reoperation was higher for THA than for HA in elderly patients with a femoral neck fracture in this retrospective study using a nationwide database.

10.
Injury ; 50(11): 2128-2135, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31530381

RESUMEN

Reconstruction of a bone defect using the Masquelet induced membrane technique has been well described. However, there are few reports of arthrodesis using this technique. In this case report, we describe a modified Masquelet technique for ankle arthrodesis with nailing. The patient was a 32-year-old man who sustained an open fracture of the right ankle with a substantial osteochondral defect as a result of a fall. Immediately after the injury, a staged procedure using the Masquelet technique was planned. The bone defect was filled with bone cement in the acute stage, but replacement of the cement was needed 6 months after the injury because of a prolonged inflammatory reaction. Ten months after the injury, the bone cement was removed, and ankle arthrodesis was performed using an IM nail with a combination of autologous and artificial bone. As a modification of the Masquelet technique, the anterior surface of the transplant site was covered with a large but thin layer of cortical bone instead of suturing the incised membrane. At 1 year postoperatively, firm bony union was achieved and the implant was removed. At follow-up 3 years after his injury, the patient is able to walk, undertake physical work, and has no clinical signs of infection. Our experience suggests that a modified induced membrane technique may be useful when treating an open limb fracture with an extensive osteochondral defect where preservation of the joint is difficult and arthrodesis is considered.


Asunto(s)
Fracturas de Tobillo/cirugía , Artrodesis/métodos , Fijación Intramedular de Fracturas/métodos , Curación de Fractura/fisiología , Fracturas Abiertas/cirugía , Osteomielitis/prevención & control , Accidentes por Caídas , Adulto , Fracturas de Tobillo/diagnóstico por imagen , Fracturas de Tobillo/fisiopatología , Antibacterianos/uso terapéutico , Trasplante Óseo , Fracturas Abiertas/diagnóstico por imagen , Fracturas Abiertas/fisiopatología , Humanos , Masculino , Resultado del Tratamiento
11.
Injury ; 50(11): 1876-1882, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31519437

RESUMEN

INTRODUCTION: The authors previously reported a CT-based nonlinear finite element analysis (nonlinear CT/FEA) model to investigate loading stress distribution in the femoral shaft of patients with atypical femoral fractures (AFFs). This showed that stress distribution, influenced primarily by femoral bowing, may determine the location of AFF. Here, we demonstrate the locational characteristics associated with AFFs in an Asian, specifically Japanese, population regarding bone strength. This is the second report from our multicentre research project suggesting a possible new concept of diagnostic criteria or treatment according to AFF subtype. PATIENTS AND METHODS: A multicentre prospective study was conducted at 12 hospitals in Japan from August 2015 through June 2018. We recruited three study groups composed of elderly females over the age of 60 years-the mid-shaft AFF group (n = 14; 80.0 ±â€¯6.5 years), the subtrochanteric AFF group (n = 15; 73.9 ±â€¯6.8 years), and the control group who had sustained unilateral hip fracture (n = 21; 82.1 ±â€¯7.1 years)-and analysed femoral neck bone density and strength. Bone strength of the femoral neck was predicted with an evaluation method using nonlinear CT/FEA in both standing and falling configuration. RESULTS: Femoral neck bone density and strength were significantly higher in the subtrochanteric AFF group compared with the mid-shaft AFF and control groups (p <  0.0001). No significant difference was seen in bone strength between the mid-shaft AFF and control groups (standing, p =  0.7616; falling, p =  0.3803). CONCLUSIONS: AFF has different features, in terms of bone strength, depending on fracture location. At the very least, Japanese patients with mid-shaft AFF could be at high risk of hip fracture because of bone fragility, in contrast to the firm bone of subtrochanteric AFF. For internal fixation of mid-shaft AFF using an IM nail, cervical screw insertion toward the femoral head might be recommended to prevent possible hip fracture.


Asunto(s)
Fracturas del Fémur/patología , Análisis de Elementos Finitos , Fracturas Osteoporóticas/patología , Tomografía Computarizada por Rayos X , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Densidad Ósea , Conservadores de la Densidad Ósea , Femenino , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/epidemiología , Humanos , Japón/epidemiología , Masculino , Fracturas Osteoporóticas/diagnóstico por imagen , Fracturas Osteoporóticas/epidemiología , Estudios Prospectivos
12.
Injury ; 48(12): 2736-2743, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28982480

RESUMEN

INTRODUCTION: Loading stress due to individual variations in femoral morphology is thought to be strongly associated with the pathogenesis of atypical femoral fracture (AFF). In Japan, studies on AFF regarding pathogenesis in the mid-shaft are well-documented and a key factor in the injury is thought to be femoral shaft bowing deformity. Thus, we developed a CT-based finite element analysis (CT/FEA) model to assess distribution of loading stress in the femoral shaft. PATIENTS AND METHODS: A multicenter prospective study was performed at 12 hospitals in Japan from August 2015 to February 2017. We assembled three study groups-the mid-shaft AFF group (n=12), the subtrochanteric AFF group (n=10), and the control group (n=11)-and analyzed femoral morphology and loading stress in the femoral shaft by nonlinear CT/FEA. RESULTS: Femoral bowing in the mid-shaft AFF group was significantly greater (lateral bowing, p<0.0001; anterior bowing, p<0.01). Femoral neck-shaft angle in the subtrochanteric AFF group was significantly smaller (p<0.001). On CT/FEA, both the mid-shaft and subtrochanteric AFF group showed maximum tensile stress located adjacent to the fracture site. Quantitatively, there was a correlation between femoral bowing and the ratio of tensile stress, which was calculated between the mid-shaft and subtrochanteric region (lateral bowing, r=0.6373, p<0.0001; anterior bowing, r=-0.5825, p<0.001). CONCLUSIONS: CT/FEA demonstrated that tensile stress by loading stress can cause AFF. The location of AFF injury could be determined by individual stress distribution influenced by femoral bowing and neck-shaft angle.


Asunto(s)
Fracturas del Fémur/patología , Fémur/patología , Fracturas por Estrés/patología , Osteoporosis/fisiopatología , Resistencia a la Tracción/fisiología , Tomografía Computarizada por Rayos X , Anciano , Densidad Ósea , Conservadores de la Densidad Ósea/uso terapéutico , Femenino , Fracturas del Fémur/diagnóstico por imagen , Fracturas del Fémur/epidemiología , Fémur/diagnóstico por imagen , Análisis de Elementos Finitos , Humanos , Japón , Masculino , Osteoporosis/diagnóstico por imagen , Osteoporosis/epidemiología , Estudios Prospectivos
13.
Injury ; 45(11): 1764-71, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25225173

RESUMEN

INTRODUCTION: Stress fractures of the bowed femoral shaft (SBFs) may be one of the causes of atypical femoral fractures (AFFs). The CT-based finite element method (CT/FEM) can be used to structurally evaluate bone morphology and bone density based on patient DICOM data, thereby quantitatively and macroscopically assessing bone strength. Here, we clarify the pathogenic mechanism of SBFs and demonstrate this new understanding of AFFs through mechanical analysis by CT/FEM. PATIENTS AND METHODS: A prospective clinical study was performed from April 2012 to February 2014. We assembled two study groups, the bowed AFF group (n=4 patients; mean age, 78.0 years) including those with a prior history of AFF associated with bowing deformity and the thigh pain group (n=14 patients; mean age, 78.6 years) comprising outpatients with complaints of thigh pain and tenderness. Stress concentration in the femoral shaft was analysed by CT/FEM, and the visual findings and extracted data were assessed to determine the maximum principal stress (MPS) and tensile stress-strength ratio (TSSR). In addition, we assessed femoral bowing, bone density, and bone metabolic markers. Wilcoxon's rank sum test was used for statistical analysis. RESULTS: All patients in the bowed AFF group showed a marked concentration of diffuse stress on the anterolateral surface. Thirteen patients in the thigh pain group had no significant findings. However, the remaining 1 patient had a finding similar to that observed in the bowed AFF group, with radiographic evidence of bowing deformity and a focally thickened lateral cortex. Patients were reclassified as having SBF (n=5) or non-SBF (n=13). Statistical analysis revealed significant differences in MPS (p=0.0031), TSSR (p=0.0022), and femoral bowing (lateral, p=0.0015; anterior, p=0.0022) between the SBF and non-SBF groups, with no significant differences in bone density or bone metabolic markers. CONCLUSIONS: Significant tensile stress due to bowing deformity can induce AFFs. SBFs should be considered a novel subtype of AFF, and patients with complaints of thigh pain and femoral shaft bowing deformity must be considered at high risk for AFFs. This project (Ref: AOTAP 13-13) was supported by AOTrauma Asia Pacific.


Asunto(s)
Fracturas del Fémur/patología , Análisis de Elementos Finitos , Fracturas por Estrés/patología , Osteoporosis/patología , Tomografía Computarizada por Rayos X , Anciano , Densidad Ósea , Conservadores de la Densidad Ósea/uso terapéutico , Femenino , Fracturas del Fémur/etiología , Fracturas del Fémur/metabolismo , Fracturas por Estrés/etiología , Fracturas por Estrés/metabolismo , Humanos , Japón/epidemiología , Masculino , Osteoporosis/complicaciones , Osteoporosis/metabolismo , Estudios Prospectivos , Población Rural
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