Wnt pathway inhibition with the porcupine inhibitor LGK974 decreases trabecular bone but not fibrosis in a murine model with fibrotic bone.

G protein-coupled receptors (GPCRs) mediate a wide spectrum of physiological functions, including the development, remodeling, and repair of the skeleton. Fibrous dysplasia (FD) of the bone is characterized by fibrotic, expansile bone lesions caused by activating mutations in GNAS. There are no effective therapies for FD. We previously showed that ColI(2.3)+/Rs1+ mice, in which Gs-GPCR signaling was hyper-activated in osteoblastic cell lineages using an engineered receptor strategy, developed a fibrotic bone phenotype with trabecularization that could be reversed by normalizing Gs-GPCR signaling, suggesting that targeting the Gs-GPCR or components of the downstream signaling pathway could serve as a promising therapeutic strategy for FD. The Wnt signaling pathway has been implicated in the pathogenesis of FD-like bone, but the specific Wnts and which cells produce them remain largely unknown. Single-cell RNA sequencing on long-bone stromal cells of 9-wk-old male ColI(2.3)+/Rs1+ mice and littermate controls showed that fibroblastic stromal cells in ColI(2.3)+/Rs1+ mice were expanded. Multiple Wnt ligands were up- or downregulated in different cellular populations, including in non-osteoblastic cells. Treatment with the porcupine inhibitor LGK974, which blocks Wnt signaling broadly, induced partial resorption of the trabecular bone in the femurs of ColI(2.3)+/Rs1+ mice, but no significant changes in the craniofacial skeleton. Bone fibrosis remained evident after treatment. Notably, LGK974 caused significant bone loss in control mice. These results provide new insights into the role of Wnt and Gs-signaling in fibrosis and bone formation in a mouse model of Gs-GPCR pathway overactivation.

Low-intensity pulsed ultrasound partially reversed the deleterious effects of a severe spinal cord injury-induced bone loss and osteoporotic fracture healing in paraplegic rats.

PURPOSE: To evaluate the effects of low-intensity pulsed ultrasound (LIPUS) on the quality of femoral fracture callus formation in rats with severe osteoporosis secondary to spinal cord injury (SCI). METHODS: Forty-five male rats were equally divided into three groups: the Sham group underwent sham surgery for SCI followed by surgery for femoral fracture on day ten post-spine surgery; the SCI group sustained a complete transection of the spinal cord and a femoral fracture ten days post-SCI; and the SCI group treated with ultrasound (SCI + US), which also sustained a femoral fracture on day ten post-SCI, concomitant with daily application of LIPUS at the fracture site. RESULTS: At the non-fractured tibias, LIPUS counteracted the SCI-induced bone loss by normalizing the osteoblastic-related gene expression, decreasing resorptive area, increasing trabecular area, and decreasing RANK and RANK-L-positive areas, which resulted in higher cortical volume and stronger tibias. Likewise, LIPUS was effective at restoring bone fracture healing in SCI rats; by promoting endochondral ossification, increasing collagen deposition and OPG-positive-area, decreasing resorptive area, which led to higher density and improved microarchitecture, ultimately resulting in stronger fracture callus. CONCLUSION: At the tibias, LIPUS counteracted the SCI-induced bone loss effects by simultaneously increasing bone formation and decreasing bone resorption. We also evidenced the osteogenic effects of LIPUS at partially restoring the endochondral ossification during callus formation, leading to a newly formed tissue with improved microarchitecture and mechanical integrity. Therefore, LIPUS may be an efficient and non-invasive approach to prevent bone loss and osteoporotic fracture in SCI individuals.

Vibration therapy as an effective approach to improve bone healing in diabetic rats.

Objective: To investigate the effects of vibration therapy on fracture healing in diabetic and non-diabetic rats. Methods: 148 rats underwent fracture surgery and were assigned to four groups: (1) SHAM: weight-matched non-diabetic rats, (2) SHAM+VT: non-diabetic rats treated with vibration therapy (VT), (3) DM: diabetic rats, and (4) DM+VT: diabetic rats treated with VT. Thirty days after diabetes induction with streptozotocin, animals underwent bone fracture, followed by surgical stabilization. Three days after bone fracture, rats began VT. Bone healing was assessed on days 14 and 28 post-fracture by serum bone marker analysis, and femurs collected for dual-energy X-ray absorptiometry, micro-computed tomography, histology, and gene expression. Results: Our results are based on 88 animals. Diabetes led to a dramatic impairment of bone healing as demonstrated by a 17% reduction in bone mineral density and decreases in formation-related microstructural parameters compared to non-diabetic control rats (81% reduction in bone callus volume, 69% reduction in woven bone fraction, 39% reduction in trabecular thickness, and 45% in trabecular number). These changes were accompanied by a significant decrease in the expression of osteoblast-related genes (Runx2, Col1a1, Osx), as well as a 92% reduction in serum insulin-like growth factor I (IGF-1) levels. On the other hand, resorption-related parameters were increased in diabetic rats, including a 20% increase in the callus porosity, a 33% increase in trabecular separation, and a 318% increase in serum C terminal telopeptide of type 1 collagen levels. VT augmented osteogenic and chondrogenic cell proliferation at the fracture callus in diabetic rats; increased circulating IGF-1 by 668%, callus volume by 52%, callus bone mineral content by 90%, and callus area by 72%; and was associated with a 19% reduction in circulating receptor activator of nuclear factor kappa beta ligand (RANK-L). Conclusions: Diabetes had detrimental effects on bone healing. Vibration therapy was effective at counteracting the significant disruption in bone repair induced by diabetes, but did not improve fracture healing in non-diabetic control rats. The mechanical stimulus not only improved bone callus quality and quantity, but also partially restored the serum levels of IGF-1 and RANK-L, inducing bone formation and mineralization, thus creating conditions for adequate fracture repair in diabetic rats.

Systemic effects of BMP2 treatment of fractures on non-injured skeletal sites during spaceflight.

Unloading associated with spaceflight results in bone loss and increased fracture risk. Bone morphogenetic protein 2 (BMP2) is known to enhance bone formation, in part, through molecular pathways associated with mechanical loading; however, the effects of BMP2 during spaceflight remain unclear. Here, we investigated the systemic effects of BMP2 on mice sustaining a femoral fracture followed by housing in spaceflight (International Space Station or ISS) or on Earth. We hypothesized that in spaceflight, the systemic effects of BMP2 on weight-bearing bones would be blunted compared to that observed on Earth. Nine-week-old male mice were divided into four groups: 1) Saline+Earth; 2) BMP+Earth; 3) Saline+ISS; and 4) BMP+ISS (n = 10 mice/group, but only n = 5 mice/group were reserved for micro-computed tomography analyses). All mice underwent femoral defect surgery and were followed for approximately 4 weeks. We found a significant reduction in trabecular separation within the lumbar vertebrae after administering BMP2 at the fracture site of mice housed on Earth. In contrast, BMP2 treatment led to a significant increase in trabecular separation concomitant with a reduction in trabecular number within spaceflown tibiae. Although these and other lines of evidence support our hypothesis, the small sample size associated with rodent spaceflight studies limits interpretations. That said, it appears that a locally applied single dose of BMP2 at the femoral fracture site can have a systemic impact on distant bones, affecting bone quantity in several skeletal sites. Moreover, our results suggest that BMP2 treatment works through a pathway involving mechanical loading in which the best outcomes during its treatment on Earth occurred in the weight-bearing bones and in spaceflight occurred in bones subjected to higher muscle contraction.

Fabrication and characterization of a bioactive polymethylmethacrylate-based porous cement loaded with strontium/calcium apatite nanoparticles.

Polymethylmethacrylate (PMMA)-based cements are used for bone reparation due to their biocompatibility, suitable mechanical properties, and mouldability. However, these materials suffer from high exothermic polymerization and poor bioactivity, which can cause the formation of fibrous tissue around the implant and aseptic loosening. Herein, we tackled these problems by adding Sr2+ -substituted hydroxyapatite nanoparticles (NPs) and a porogenic compound to the formulations, thus creating a microenvironment suitable for the proliferation of osteoblasts. The NPs resembled the structure of the bone's apatite and enabled the controlled release of Sr2+ . Trends in the X-ray patterns and infrared spectra confirmed that Sr2+ replaced Ca2+ in the whole composition range of the NPs. The inclusion of an effervescent additive reduced the polymerization temperature and lead to the formation of highly porous cement exhibiting mechanical properties comparable to the trabecular bone. The formation of an opened and interconnected matrix allowed osteoblasts to penetrate the cement structure. Most importantly, the gas formation confined the NPs at the surface of the pores, guaranteeing the controlled delivery of Sr2+ within a concentration sufficient to maintain osteoblast viability. Additionally, the cement was able to form apatite when immersed into simulated body fluids, further increasing its bioactivity. Therefore, we offer a formulation of PMMA cement with improved in vitro performance supported by enhanced bioactivity, increased osteoblast viability and deposition of mineralized matrix assigned to the loading with Sr2+ -substituted hydroxyapatite NPs and the creation of an interconnected porous structure. Altogether, our results hold promise for enhanced bone reparation guided by PMMA cements.

DIRECT PEDICLE SCREW INSERTION PULLOUT STRENGTH.

OBJECTIVE: Study the in vitro pullout strength of SpineGuard/Zavation Dynamic Surgical Guidance Z-Direct Screw (DSG Screw), a screw pedicle designed to be inserted using a direct insertion technique. METHODS: DSG Screws of 5.5 mm and 6.5 mm were introduced into polyurethane blocks with a density of 10 PCF (0,16 g/cm3). According to the experimental group, screws were inserted without pilot hole, with pilot without tapping, undertapping and line-to-line tapping. Screw pullout tests were performed using a universal test machine after screw insertion into polyurethane blocks. RESULTS: Screws inserted directly into the polyurethane blocks without pilot hole and tapping showed a statistically higher pullout strength. Insertion of the screw without tapping or with undertapping increases the pullout screw strength compared to line-to-line tapping. CONCLUSION: DSG Screw showed the highest pullout strength after its insertion without pilot hole and tapping. Level of Evidence V, Expert Opinion.

OBJETIVO: Estudar a resistência ao arrancamento in vitro do parafuso de inserção direta da SpineGuard/Zavation (parafuso DSG), um parafuso pedicular projetado para ser inserido usando a técnica de inserção direta. MÉTODOS: Parafusos DSG de 5,5 mm e 6,5 mm foram introduzidos em blocos de poliuretano com densidade de 10 PCF (0,16 g/cm3). De acordo com o grupo experimental, os parafusos foram inseridos sem orifício piloto, com orifício e sem macheamento e macheamento diâmetro inferior com mesma geometria. Os testes de resistência dos parafusos foram realizados usando uma máquina de teste universal após a inserção dos parafusos nos blocos de poliuretano. RESULTADOS: Os parafusos inseridos diretamente nos blocos de poliuretano sem orifício piloto e sem macheamento apresentaram uma resistência de arrancamento com significância estatística maior. A inserção do parafuso sem macheamento ou com macheamento com diâmetro inferior apresenta maior resistência ao arrancamento em comparação com o macheamento do mesmo diâmetro. CONCLUSÃO: O parafuso DSG apresentou a maior resistência ao arrancamento após sua inserção sem orifício piloto e sem macheamento. Nível de Evidência V, Opinião do Especialista.

Direct pedicle screw insertion pullout strength / Resistência ao arrancamento do parafuso pedicular de inserção direta

ABSTRACT Objective: Study the in vitro pullout strength of SpineGuard/Zavation Dynamic Surgical Guidance Z-Direct Screw (DSG Screw), a screw pedicle designed to be inserted using a direct insertion technique. Methods: DSG Screws of 5.5 mm and 6.5 mm were introduced into polyurethane blocks with a density of 10 PCF (0,16 g/cm3). According to the experimental group, screws were inserted without pilot hole, with pilot without tapping, undertapping and line-to-line tapping. Screw pullout tests were performed using a universal test machine after screw insertion into polyurethane blocks. Results: Screws inserted directly into the polyurethane blocks without pilot hole and tapping showed a statistically higher pullout strength. Insertion of the screw without tapping or with undertapping increases the pullout screw strength compared to line-to-line tapping. Conclusion: DSG Screw showed the highest pullout strength after its insertion without pilot hole and tapping. Level of Evidence V, Expert Opinion.

RESUMO Objetivo: Estudar a resistência ao arrancamento in vitro do parafuso de inserção direta da SpineGuard/Zavation (parafuso DSG), um parafuso pedicular projetado para ser inserido usando a técnica de inserção direta. Métodos: Parafusos DSG de 5,5 mm e 6,5 mm foram introduzidos em blocos de poliuretano com densidade de 10 PCF (0,16 g/cm3). De acordo com o grupo experimental, os parafusos foram inseridos sem orifício piloto, com orifício e sem macheamento e macheamento diâmetro inferior com mesma geometria. Os testes de resistência dos parafusos foram realizados usando uma máquina de teste universal após a inserção dos parafusos nos blocos de poliuretano. Resultados: Os parafusos inseridos diretamente nos blocos de poliuretano sem orifício piloto e sem macheamento apresentaram uma resistência de arrancamento com significância estatística maior. A inserção do parafuso sem macheamento ou com macheamento com diâmetro inferior apresenta maior resistência ao arrancamento em comparação com o macheamento do mesmo diâmetro. Conclusão: O parafuso DSG apresentou a maior resistência ao arrancamento após sua inserção sem orifício piloto e sem macheamento. Nível de Evidência V, Opinião do Especialista.

Gene-metabolite networks associated with impediment of bone fracture repair in spaceflight.

Adverse effects of spaceflight on musculoskeletal health increase the risk of bone injury and impairment of fracture healing. Its yet elusive molecular comprehension warrants immediate attention, since space travel is becoming more frequent. Here we examined the effects of spaceflight on bone fracture healing using a 2 mm femoral segmental bone defect (SBD) model. Forty, 9-week-old, male C57BL/6J mice were randomized into 4 groups: 1) Sham surgery on Ground (G-Sham); 2) Sham surgery housed in Spaceflight (FLT-Sham); 3) SBD surgery on Ground (G-Surgery); and 4) SBD surgery housed in Spaceflight (FLT-Surgery). Surgery procedures occurred 4 days prior to launch; post-launch, the spaceflight mice were house in the rodent habitats on the International Space Station (ISS) for approximately 4 weeks before euthanasia. Mice remaining on the Earth were subjected to identical housing and experimental conditions. The right femur from half of the spaceflight and ground groups was investigated by micro-computed tomography (µCT). In the remaining mice, the callus regions from surgery groups and corresponding femoral segments in sham mice were probed by global transcriptomic and metabolomic assays. µCT confirmed escalated bone loss in FLT-Sham compared to G-Sham mice. Comparing to their respective on-ground counterparts, the morbidity gene-network signal was inhibited in sham spaceflight mice but activated in the spaceflight callus. µCT analyses of spaceflight callus revealed increased trabecular spacing and decreased trabecular connectivity. Activated apoptotic signals in spaceflight callus were synchronized with inhibited cell migration signals that potentially hindered the wound site to recruit growth factors. A major pro-apoptotic and anti-migration gene network, namely the RANK-NFκB axis, emerged as the central node in spaceflight callus. Concluding, spaceflight suppressed a unique biomolecular mechanism in callus tissue to facilitate a failed regeneration, which merits a customized intervention strategy.

Analysis of the effects of spaceflight and local administration of thrombopoietin to a femoral defect injury on distal skeletal sites.

With increased human presence in space, bone loss and fractures will occur. Thrombopoietin (TPO) is a recently patented bone healing agent. Here, we investigated the systemic effects of TPO on mice subjected to spaceflight and sustaining a bone fracture. Forty, 9-week-old, male, C57BL/6 J were divided into 4 groups: (1) Saline+Earth; (2) TPO + Earth; (3) Saline+Flight; and (4) TPO + Flight (n = 10/group). Saline- and TPO-treated mice underwent a femoral defect surgery, and 20 mice were housed in space ("Flight") and 20 mice on Earth for approximately 4 weeks. With the exception of the calvarium and incisor, positive changes were observed in TPO-treated, spaceflight bones, suggesting TPO may improve osteogenesis in the absence of mechanical loading. Thus, TPO, may serve as a new bone healing agent, and may also improve some skeletal properties of astronauts, which might be extrapolated for patients on Earth with restraint mobilization and/or are incapable of bearing weight on their bones.

Association of Urinary and Blood Concentrations of Heavy Metals with Measures of Bone Mineral Density Loss: a Data Mining Approach with the Results from the National Health and Nutrition Examination Survey.

Osteoporosis and its consequence of fragility fracture represent a major public health problem. Human exposure to heavy metals has received considerable attention over the last decades. However, little is known about the influence of co-exposure to multiple heavy metals on bone density. The present study aimed to examine the association between exposure to metals and bone mineral density (BMD) loss. Blood and urine concentrations of 20 chemical elements were selected from 3 cycles (2005-2010) NHANES (National Health and Nutrition Examination Survey), in which we included white women over 50 years of age and previously selected for BMD testing (N = 1892). The bone loss group was defined as participants having T-score < - 1.0, and the normal group was defined as participants having T-score ≥ - 1.0. We developed classification models based on support vector machines capable of determining which factors could best predict BMD loss. The model which included the five-best features-selected from the random forest were age, body mass index, urinary concentration of arsenic (As), cadmium (Cd), and tungsten (W), which have achieved high scores for accuracy (92.18%), sensitivity (90.50%), and specificity (93.35%). These data demonstrate the importance of these factors and metals to the classification since they alone were capable of generating a classification model with a high prediction of accuracy without requiring the other variables. In summary, our findings provide insight into the important, yet overlooked impact that arsenic, cadmium, and tungsten have on overall bone health.

Review of Secondary Causes of Osteoporotic Fractures Due to Diabetes and Spinal Cord Injury.

PURPOSE OF REVIEW: The aim of this review is to gain a better understanding of osteoporotic fractures and the different mechanisms that are driven in the scenarios of bone disuse due to spinal cord injury and osteometabolic disorders due to diabetes. RECENT FINDINGS: Despite major advances in understanding the pathogenesis, prevention, and treatment of osteoporosis, the high incidence of impaired fracture healing remains an important complication of bone loss, leading to marked impairment of the health of an individual and economic burden to the medical system. This review underlines several pathways leading to bone loss and increased risk for fractures. Specifically, we addressed the different mechanisms leading to bone loss after a spinal cord injury and diabetes. Finally, it also encompasses the changes responsible for impaired bone repair in these scenarios, which may be of great interest for future studies on therapeutic approaches to treat osteoporosis and osteoporotic fractures.

Gene expression changes are associated with severe bone loss and deficient fracture callus formation in rats with complete spinal cord injury.

STUDY DESIGN: Animal study. OBJECTIVES: To investigate the effects of SCI on bone quality and callus formation. SETTING: University and hospital-based research center, Ribeirão Preto Medical School, Brazil. METHODS: Rats sustaining a complete SCI for 10 days received a fracture at the femoral diaphysis and were followed-up for 14 days. Bone callus and contralateral nonfractured tibia were assessed by DXA, µCT, ELISA, histomorphometry, immunohistochemistry, biomechanical test, and gene expression. RESULTS: SCI downregulated osteoblastic-related gene expression in the nonfractured tibias, associated with a twofold increase in osteoclasts and overexpression of RANK/RANKL, which resulted in lower bone mass, impaired microarchitecture, and weaker bones. On day 14 postfracture, we revealed early and increased trabecular formation in the callus of SCI rats, despite a marked 75% decrease in OPG-positive cells, and 41% decrease in density. Furthermore, these calluses showed higher porosity and thinner newly formed trabeculae, leading to lower strength and angle failure. CONCLUSIONS: SCI-induced bone loss resulted from increased bone resorption and decreased bone formation. We also evidenced accelerated bone healing in the SCI rats, which may be attributed to the predominant intramembranous ossification. However, the newly formed bone was thinner, less dense, and more porous than those in the non-SCI rats. As a result, these calluses are weaker and tolerate lesser torsion deformation than the controls, which may result in recurrent fractures and characterizes a remarkable feature that may severely impair life quality.

The effects of spaceflight and fracture healing on distant skeletal sites.

Spaceflight results in reduced mechanical loading of the skeleton, which leads to dramatic bone loss. Low bone mass is associated with increased fracture risk, and this combination may compromise future, long-term, spaceflight missions. Here, we examined the systemic effects of spaceflight and fracture surgery/healing on several non-injured bones within the axial and appendicular skeleton. Forty C57BL/6, male mice were randomized into the following groups: (1) Sham surgery mice housed on the earth (Ground + Sham); (2) Femoral segmental bone defect surgery mice housed on the earth (Ground + Surgery); (3) Sham surgery mice housed in spaceflight (Flight + Sham); and (4) Femoral segmental bone defect surgery mice housed in spaceflight (Flight + Surgery). Mice were 9 weeks old at the time of launch and were euthanized approximately 4 weeks after launch. Micro-computed tomography (µCT) was used to evaluate standard bone parameters in the tibia, humerus, sternebra, vertebrae, ribs, calvarium, mandible, and incisor. One intriguing finding was that both spaceflight and surgery resulted in virtually identical losses in tibial trabecular bone volume fraction, BV/TV (24-28% reduction). Another important finding was that surgery markedly changed tibial cortical bone geometry. Understanding how spaceflight, surgery, and their combination impact non-injured bones will improve treatment strategies for astronauts and terrestrial humans alike.

Undernutrition impairs the quality of growth plate and trabecular and cortical bones in growing rats1.

PURPOSE: To investigate the effects of dietary restriction on the growth plate and long bone tissue in growing rats. METHODS: Sixty male Wistar rats were randomly assigned to two groups: Control (Con) and Diet-restricted (Res). After weaning, the Res rats were offered 50% of the chow ingested by the control (ad libitum food intake). The animals were subdivided into two subgroups with follow-ups up to 56 or 70 days. After euthanasia, the growth plate of tibias was analyzed by histomorphometry, micro-computed tomography, and mechanical test. The trabecular and compact bones were evaluated by histomorphometry, dual-energy X-ray absorptiometry, and micro-computed tomography (µCT). Real-time PCR was used to analyze gene expression. RESULTS: Although dietary restriction did not alter gene expression, several phenotypic changes were seen in the growth plate; i.e., decrease in volume, reduction in total area and height, decrease in the area ossified zones, mechanical weakening, reduction in mass of trabecular and cortical bone, lower bone density, deterioration of the trabecular and cortical microarchitecture, and trabeculae with lower collagen deposition. CONCLUSION: Dietary restriction had severe detrimental effects on the growth plate and trabecular and cortical bone.

Bone callus formation is highly disrupted by dietary restriction in growing rats sustaining a femoral fracture1.

PURPOSE: To evaluate the effects of food restriction on fracture healing in growing rats. METHODS: Sixty-eight male Wistar rats were assigned to two groups: (1) Control and (2) Dietary restriction. After weaning the dietary restricted animals were fed ad libitum for 42 days with 50% of the standard chow ingested by the control group. Subsequently, the animals underwent bone fracture at the diaphysis of the right femur, followed by surgical stabilization of bone fragments. On days 14 and 28 post-fracture, the rats were euthanized, and the fractured femurs were dissected, the callus was analyzed by dual-energy X-ray absorptiometry, micro-computed tomography, histomorphometry, mechanical tests, and gene expression. RESULTS: Dietary restriction decreased body mass gain and resulted in several phenotypic changes at the bone callus (a delay in cell proliferation and differentiation, lower rate of newly formed bone and collagen deposition, reductions in bone callus density and size, decrease in tridimensional callus volume, deterioration in microstructure, and reduction in bone callus strength), together with the downregulated expression of osteoblast-related genes. CONCLUSION: Dietary restriction had detrimental effects on osseous healing, with a healing delay and a lower quality of bone callus formation.

Bone callus formation is highly disrupted by dietary restriction in growing rats sustaining a femoral fracture

Abstract Purpose: To evaluate the effects of food restriction on fracture healing in growing rats. Methods: Sixty-eight male Wistar rats were assigned to two groups: (1) Control and (2) Dietary restriction. After weaning the dietary restricted animals were fed ad libitum for 42 days with 50% of the standard chow ingested by the control group. Subsequently, the animals underwent bone fracture at the diaphysis of the right femur, followed by surgical stabilization of bone fragments. On days 14 and 28 post-fracture, the rats were euthanized, and the fractured femurs were dissected, the callus was analyzed by dual-energy X-ray absorptiometry, micro-computed tomography, histomorphometry, mechanical tests, and gene expression. Results: Dietary restriction decreased body mass gain and resulted in several phenotypic changes at the bone callus (a delay in cell proliferation and differentiation, lower rate of newly formed bone and collagen deposition, reductions in bone callus density and size, decrease in tridimensional callus volume, deterioration in microstructure, and reduction in bone callus strength), together with the downregulated expression of osteoblast-related genes. Conclusion: Dietary restriction had detrimental effects on osseous healing, with a healing delay and a lower quality of bone callus formation.

Undernutrition impairs the quality of growth plate and trabecular and cortical bones in growing rats

Abstract Purpose: To investigate the effects of dietary restriction on the growth plate and long bone tissue in growing rats. Methods: Sixty male Wistar rats were randomly assigned to two groups: Control (Con) and Diet-restricted (Res). After weaning, the Res rats were offered 50% of the chow ingested by the control (ad libitum food intake). The animals were subdivided into two subgroups with follow-ups up to 56 or 70 days. After euthanasia, the growth plate of tibias was analyzed by histomorphometry, micro-computed tomography, and mechanical test. The trabecular and compact bones were evaluated by histomorphometry, dual-energy X-ray absorptiometry, and micro-computed tomography (μCT). Real-time PCR was used to analyze gene expression. Results: Although dietary restriction did not alter gene expression, several phenotypic changes were seen in the growth plate; i.e., decrease in volume, reduction in total area and height, decrease in the area ossified zones, mechanical weakening, reduction in mass of trabecular and cortical bone, lower bone density, deterioration of the trabecular and cortical microarchitecture, and trabeculae with lower collagen deposition. Conclusion: Dietary restriction had severe detrimental effects on the growth plate and trabecular and cortical bone.

Nandrolone decanoate appears to increase bone callus formation in young adult rats after a complete femoral fracture.

PURPOSE: To evaluate the influence of nandrolone decanoate on fracture healing and bone quality in normal rats. METHODS: Male rats were assigned to four groups (n=28/group): Control group consisting of animals without any intervention, Nandrolone decanoate (DN) group consisting of animals that received intramuscular injection of nandrolone decanoate, Fracture group consisting of animals with a fracture at the mid-diaphysis of the femur, and Fracture and nandrolone decanoate group consisting of animals with a femur fracture and treatment with nandrolone decanoate. Fractures were created at the mid-diaphysis of the right femur by a blunt trauma and internally fixed using an intramedullary steel wire. The DN was injected intramuscularly twice per week (10 mg/kg of body mass). The femurs were measured and evaluated by densitometry and mechanical resistance after animal euthanasia. The newly formed bone and collagen type I levels were quantified in the callus. RESULTS: The treated animals had longer femurs after 28 days. The quality of the intact bone was not significantly different between groups. The bone callus did show a larger mass in the treated rats. CONCLUSION: The administration of nandrolone decanoate did not affect the quality of the intact bone, but might have enhanced the bone callus formation.

Nandrolone decanoate appears to increase bone callus formation in young adult rats after a complete femoral fracture

Abstract Purpose: To evaluate the influence of nandrolone decanoate on fracture healing and bone quality in normal rats. Methods: Male rats were assigned to four groups (n=28/group): Control group consisting of animals without any intervention, Nandrolone decanoate (DN) group consisting of animals that received intramuscular injection of nandrolone decanoate, Fracture group consisting of animals with a fracture at the mid-diaphysis of the femur, and Fracture and nandrolone decanoate group consisting of animals with a femur fracture and treatment with nandrolone decanoate. Fractures were created at the mid-diaphysis of the right femur by a blunt trauma and internally fixed using an intramedullary steel wire. The DN was injected intramuscularly twice per week (10 mg/kg of body mass). The femurs were measured and evaluated by densitometry and mechanical resistance after animal euthanasia. The newly formed bone and collagen type I levels were quantified in the callus. Results: The treated animals had longer femurs after 28 days. The quality of the intact bone was not significantly different between groups. The bone callus did show a larger mass in the treated rats. Conclusion: The administration of nandrolone decanoate did not affect the quality of the intact bone, but might have enhanced the bone callus formation.