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Long-Term Response to a Bioactive Biphasic Biomaterial in the Femoral Neck of Osteoporotic Rats.

ABSTRACT: Osteoporosis often leads to fragility fractures of the hip, resulting in impaired quality of life and increased mortality. Augmenting the proximal femur could be an attractive option for prevention of fracture or fixation device failure. We describe a tissue engineering based strategy to enhance long-term bone formation in the femoral neck of osteoporotic rats by locally delivering bioactive molecules; recombinant human bone morphogenic protein-2 (rhBMP-2), and zoledronic acid (ZA) by using a calcium sulfate/hydroxyapatite (CaS/HA) biomaterial. A defect was created by reaming the femoral neck canal of osteoporotic (OVX) rats and they were treated as follows: G1. Empty, G2. CaS/HA, G3. CaS/HA+Systemic ZA, G4. CaS/HA+Local ZA, and G5. CaS/HA+Local ZA+rhBMP-2. Bone formation was evaluated 6 months after treatment. Further, radioactively labeled 14C-ZA was used to study the bioavailability of ZA at the defect location, which was determined by using scintillation counting. Micro-CT indicated significantly higher bone volume in groups G4 and G5 compared with the other treatment groups. This was confirmed qualitatively by histological assessment. Addition of rhBMP-2 gave no additional benefit in this model. Local delivery of ZA performed better than systemic administration of ZA. Mechanical testing showed no differences between the groups, likely reflecting that the addition of bioactive molecules had limited effect on cortical bone or the choice of mechanical testing setup was not optimal. Scintillation counting revealed higher amounts of 14C-ZA present in the treated leg of G4 compared with its contralateral control and compared with G3, indicating that local ZA delivery can be used to achieve high local concentrations without causing a systemic effect. This long-term study shows that local delivery of ZA using a CaS/HA carrier can regenerate cancellous bone in the femoral neck canal and has clear implications for enhancing implant integration and fixation in fragile bone.

SUBMITTER: Raina DB

PROVIDER: S-EPMC7580608 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Long-Term Response to a Bioactive Biphasic Biomaterial in the Femoral Neck of Osteoporotic Rats.

Raina Deepak Bushan DB Širka Aurimas A Qayoom Irfan I Teotia Arun Kumar AK Liu Yang Y Tarasevicius Sarunas S Tanner Kathleen Elizabeth KE Isaksson Hanna H Kumar Ashok A Tägil Magnus M Lidgren Lars L

Tissue engineering. Part A 20201001 19-20

Osteoporosis often leads to fragility fractures of the hip, resulting in impaired quality of life and increased mortality. Augmenting the proximal femur could be an attractive option for prevention of fracture or fixation device failure. We describe a tissue engineering based strategy to enhance long-term bone formation in the femoral neck of osteoporotic rats by locally delivering bioactive molecules; recombinant human bone morphogenic protein-2 (rhBMP-2), and zoledronic acid (ZA) by using a ca ...[more]

PMID: 32242474

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Project description:Osteoporosis is the consequence of altered bone metabolism resulting in the systemic reduction of bone strength and increased risk of fragility fractures. MicroRNAs (miRNAs) regulate gene expression on a post-transcriptional level are known to take part in the control of bone formation and bone resorption. Recently, targeted secretion of miRNAs from cells originating from various tissues has been described, which allows for their minimal-invasive detection in serum/plasma and use as biomarkers for presence and progression of pathological conditions. One pilot study has reported circulating miRNAs in serum and tissue of fracture patients. However, further studies are required to explore whether a dysbalance in bone homeostasis of fracture patients can reliably be reflected by specific circulating miRNAs, and whether these miRNAs might serve as drugable targets. Here, we report results from a comprehensive multiplex study of 175 miRNAs in serum samples obtained from 7 patients with osteoporotic fractures at the femoral neck, and 7 age-matched controls. Following elaborate quality control statistical analysis of this exploratory dataset identified 9 microRNAs with altered serum levels in response to fracture (adjusted p-value < 0.1). Of these, hsa-miR-10a/b gave excellent discrimination of both groups (AUC = 1.0), and clustering of samples based on the top10 miRNAs confirmed the high discriminatory power of circulating microRNAs for osteoporotic fractures. In the next step 3 miRNAs with unknown roles in osteogenic differentiation and 4 miRNA from a previous study were tested for their effects on osteogenic differentiation. Of these, 3 miRNAs showed robust effects on osteogenic differentiation. Overall, these data provide important insights into changes in serum miRNA in post-traumatic patients. Future studies will show, whether this knowledge can be used to improve current diagnostic methodologies to predict fracture risk and design novel treatment strategies for osteoporosis patients.

Project description:The aim of this study was to monitor long-term changes in bone mineral density (BMD) after menopause and factors affecting BMD. The study population consisted of a random sample of 3222 women from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study, of which 62.1% were postmenopausal at the beginning of the study. This group of women underwent dual-energy X-ray absorptiometry (DXA) measurements at the femoral neck every 5 years from baseline (in 1989) up to 25-year follow-up. They also responded to risk-factor questionnaires at 5-year intervals. During the 25-year follow-up, the baseline cohort decreased to 686 women. The women were divided into quartiles based on their baseline BMD. Self-reported hormone replacement therapy (HRT) and corticosteroid use were divided into ever users and never users. Morbidity was assessed as the total number of self-reported diseases and BMD-affecting diseases. The mean 25-year BMD change was found to be -10.1%, p < 0.001. Higher baseline BMD was associated with higher bone loss rate; the reduction in the highest quartile BMD was 11.1% and in the lowest quartile 7.4% (p = 0.0031). Lower baseline body mass index (BMI) and a greater increase in BMI were found to protect against postmenopausal bone loss (p < 0.001). The lowest bone loss quartile included 15.2% more HRT users than the highest bone loss quartile (p = 0.004). The number of diseases/bone-affecting diseases, use of vitamin D/calcium supplementation, use of corticosteroids, smoking or alcohol use had no statistical significance for annual bone loss rate. This study presents hitherto the longest (25-year) BMD follow-up in postmenopausal women. The linear femoral neck bone loss of 10% was less than previously assumed. A 5-year BMD change appeared to predict long-term bone loss in postmenopausal women. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Project description:ObjectivesTo evaluate the long-term efficacy of cannulated internal fixation in patients who sustain femoral neck fracture (FNF) and risk factors influencing the outcomes.MethodsThis retrospective study analyzed data from 73 elderly patients aged ≥60 years old, hospitalized for FNF and treated with cannulated internal fixation between August 2008 and July 2016. The inclusion criteria were: (i) patients aged ≥60 years; (ii) patients with recent femoral neck fracture, with times of injury ranging from 12-72 h; and (iii) patients who underwent Garden II-IV closed reduction and internal fixation. Patients were classified based on the Garden fracture type and Pauwels angle. Clinical data and radiographs before and after the surgery were collected. Subsequently, surgery was performed with the patient in supine position, under general or lumbar epidural anesthesia. Closed reduction was performed until satisfactory fracture reduction quality was achieved. The weight of all included patients were <75 kg, and thus, minimal internal fixation was performed. The ischemic necrosis of the femoral head was diagnosed by considering the symptoms, signs, and radiological findings. Harris hip scores were used to evaluate postoperative recovery of hip function. Furthermore, relationships between Garden fracture type and necrosis rate of the femoral head, Pauwels angle and necrosis rate of the femoral head, Garden fracture type and Harris hip score, and age and Harris hip score were analyzed.ResultsThe mean duration of surgery was 1 ± 0.17 h and blood loss for all the patients was approximately 15 mL. The included patients were followed up for 13-128 months, with an average follow-up of 61 months. Among the included 73 patients, 65 (89.0%) exhibited satisfactory union, seven (9.6%) had femoral head necrosis, and one (1.4%) had nonunion. For seven patients with femoral head necrosis, there were two, two, and three patients classified as Garden IV, Garden III, and Garden II, respectively, and two and five patients classified as Pauwels II and Pauwels III, respectively. Among the seven cases, four underwent hip replacement. Garden fracture type was not significantly associated with femoral head necrosis (χ2 = 0.44, P > 0.05) or Harris score (χ2 = 1.43, P > 0.05). Patients with Pauwels I (0%) and II (4.3%) fractures exhibited a significantly lower necrosis rate than those with Pauwels III fractures (41.7%) (P < 0.05).ConclusionsCannulated internal fixation was more suitable for older Chinese patients with Pauwels I/II fractures than those with Pauwels III fractures.

Project description:BackgroundRecent studies have described unique clinical and radiographic characteristics of femoral stress fractures or low-energy fractures associated with long-term bisphosphonate therapy. However, it is unclear whether these fractures require subsequent surgery after the initial treatment.Questions/purposesWe performed a cohort analysis of bisphosphonate-associated femoral stress fractures to (1) confirm the unique clinical and radiographic findings compared with existing literature, (2) determine whether any patients with completed fractures had no preexisting transverse stress fracture lines, (3) assess the need for additional surgical procedures, and (4) determine whether the hospital length of stay (LOS) differed for patients with prophylactic fixation of stress fractures versus fixation of completed fractures.MethodsWe retrospectively reviewed 16 patients with 24 diaphyseal and subtrochanteric femoral stress fractures (14) or low-energy fractures (10) who had been on bisphosphonates for 3 to 10 years. Data included demographics, symptoms, medication history, radiographic characteristics, treatment parameters, LOS, and outcome. Minimum followup was 9 months (average, 44.0 months; median, 31 months; range, 9-112 months).ResultsAll patients had clinical and radiographic findings similar to those reported in the literature. Two of four patients sustained completed fractures after radiographs failed to reveal transverse lateral fracture lines. None of the 14 prophylactically treated impending fractures progressed or required additional surgery; however, in five of 10 femurs treated after fracture completion, six additional surgeries were performed. The average hospital LOS was shorter in patients who underwent prophylactic fixation (3.8 days) than in patients treated for completed fractures (5.6 days).ConclusionsBisphosphonate-associated stress fractures and completed fractures are unique, possessing subtle characteristic radiographic features. Completed fractures may occur through the thickened bone in the absence of an appreciable transverse stress fracture line. Our observations suggest prophylactic reconstruction nail fixation may avoid fracture completion and may be associated with a shorter hospital LOS and less morbidity than treatment of completed fractures.Level of evidenceLevel IV, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Project description:BACKGROUND:Atypical femoral fracture is one of the many complications after the long-term use of bisphosphonates. The American Society for Bone and Mineral Research has officially excluded periprosthetic femoral fractures (PFFs) from the definition of atypical femoral fractures (AFFs). Several case reports found that PFFs can occur with characteristics similar to those of AFFs. The purpose of our study was to evaluate the proportion of atypical fractures among Vancouver type B1 fractures, and to determine the association between the long-term use of bisphosphonates and the occurrence of atypical periprosthetic femoral fractures (APFFs). METHODS:In this retrospective study, we reviewed 41 patients with Vancouver type B1 periprosthetic fractures between January 1, 2011 and December 31, 2018. We classified them into two groups, namely atypical and typical PFFs, based on the fracture morphology. We noted the proportion of atypical periprosthetic fractures among B1 fractures and identified risk factors. RESULTS:Among the 41 PFFs, 5 (13%) fractures were classified as atypical PFF based on the radiological characteristics. The longer duration of bisphosphonate use was probably the only independent risk factor that significantly increases the occurrence of APFF (p?=?0.03, 0.08 (CI 0.008 - 0.16)). There were no significant differences in age, gender, body mass index, comorbidities, corticosteroid use, positioning of the femoral stem, the method of fixation (cemented or cementless) and time lapse from before the primary prosthesis implantation to the PFF in the development of atypical fracture type. CONCLUSIONS:There seems to be a correlation between the long-term intake of bisphosphonates and the atypical periprosthetic fracture. Atypical femoral fracture can also occur in the periprosthetic form. TRIAL REGISTRATION:Study number: 22/2019-SZTE, http://www.klinikaikutatas.hu/hu/kutatasetika/jovahagyott-vizsgalatok-koezerdeku-adatai/category/25-jovahagyott-vizsgalatok-kozerdeku-adatai-rkeb-2019.html?download=985:22-2019 .

Project description:BackgroundHip fracture is associated with pronounced morbidity and excess mortality in elderly women with postmenopausal osteoporosis. Many drugs have been developed to treat osteoporosis and to reduce the risk of osteoporotic fractures. We investigated the effects of combined alendronate and vitamin D3 treatment on bone mass and fracture load at the femoral neck in ovariectomized (OVX) rats, and evaluated the relationship between bone mass parameters and femoral neck strength.MethodsThirty 12-week-old female rats underwent either a sham-operation (n = 6) or OVX (n = 24). Twenty weeks later, OVX rats were further divided into four groups and received daily doses of either saline alone, 0.1 mg/kg alendronate, 0.1 microg/kg calcitriol, or a combination of both two drugs by continuous infusion via Alzet mini-osmotic pumps. The sham-control group received saline alone. After 12 weeks of treatment, femoral necks were examined using peripheral quantitative computed tomography (pQCT) densitometry and mechanical testing.ResultsSaline-treated OVX rats showed significant decreases in total bone mineral content (BMC) (by 28.1%), total bone mineral density (BMD) (by 9.5%), cortical BMC (by 26.3%), cancellous BMC (by 66.3%), cancellous BMD (by 29.0%) and total cross-sectional bone area (by 30.4%) compared with the sham-control group. The combined alendronate and calcitriol treatments improved bone loss owing to estrogen deficiency. On mechanical testing, although OVX significantly reduced bone strength of the femoral neck (by 29.3%) compared with the sham-control group, only the combined treatment significantly improved the fracture load at the femoral neck in OVX rats to the level of the sham-controls. The correlation of total BMC to fracture load was significant, but that of total BMD was not.ConclusionOur results showed that the combined treatment with alendronate and calcitriol significantly improved bone fragility of the femoral neck in OVX osteopenic rats.

Dataset Information

Long-Term Response to a Bioactive Biphasic Biomaterial in the Femoral Neck of Osteoporotic Rats.

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Long-Term Response to a Bioactive Biphasic Biomaterial in the Femoral Neck of Osteoporotic Rats.

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