Biological Healing of Large Diaphyseal Deep-frozen Allograft Transplants

The biological healing of large, deep-frozen, diaphyseal allografts was studied in 24 cats. Deep-frozen allograft stored at –80°C was used to replace a large defect, at least two-thirds of the cat's tibial diaphysis. Intra-medullary rod fixation was used. The healing was studied at observation periods of 4, 6, 8, 12, 16, 24 and 36 weeks. Biological parameters studied included microangiography for revascularisation and fracture healing, bone resorption, new bone formation and callus encasement. Deep-frozen allografts united without difficulty by 12 weeks. However, minimal revascularisation of the allograft occurred even at 9 months. Likewise, minimal biological repair activity was seen even at 9 months as shown by the parameters of bone resorption, cortical new bone formation and callus encasement. Biologically, deep-frozen cortical allografts remained inert for a long period of time in the adult cat.     

Processing of Whole Femoral Head Allografts: A Method for Improving Clinical Efficacy and Safety

Femoral heads removed during primary hip replacement surgery are widely utilised as a source of allograft bone. Despite evidence that processing these grafts to remove blood and marrow elements improves both the clinical performance and safety of these allografts, many are transplanted without any processing being applied at all. The goal of this study was to investigate the efficiency of an allograft processing protocol which incorporates pasteurisation, (3h, 56–60°C) centrifugation, (1850g, 2 × 15min, 40°C) sonication, and repeated washing in warm (56–60°C, 19h) distilled, sterile water to remove blood and marrow elements from the graft. The protocol also involves applying heat treatment to the grafts which has been demonstrated to inactivate many pathogenic viruses. Following the processing procedure, the grafts are lyophilised and sterilised with ethylene oxide gas. The amount and rate of removal of 4 different components of blood and marrow from 6 whole femoral head allografts were measured. These were lipid, soluble protein, elastase and chloride ions. Lipid removal was assessed gravimetrically by solvent extraction of dried samples, soluble protein by the Bradford assay, elastase by radioimmunoassay and choride ion content by a modified commercially available colorimetric assay. Removing lipid from grafts has been shown to increase the rate of incorporation when the graft is used clinically. Elastase was studied as a marker of leukocyte removal, as evidence suggests the majority of potentially infective transmissible spongiform encephalopathy (TSE) activity resides in a sub-population of leukocytes. Soluble protein was studied as a marker of plasma removal, as a smaller amount of TSE infectivity resides here. Chloride removal was measured as this is a necessary pre-requisite to terminal sterilisation with ethylene oxide. The results showed that the protocol removed 74.5% (range: 68.0–90.8) of the lipid content, 96.4% (range: 94.8–98.4) of the soluble protein content, 97.7% (range: 97.1–100) of the elastase content and 98.8% (range: 98.0–99.2) of the chloride ion content. We have shown that processing designed to improve the clinical efficiency and safety of bone allografts can be accomplished without compromising the structural and biological properties of the graft.     

Effect of sclerostin-neutralising antibody on periarticular and systemic bone in a murine model of rheumatoid arthritis: a microCT study

Introduction

Patients with chronic inflammatory diseases have increased bone loss and bone fragility and are at increased risk of fracture. Although anti-resorptive drugs are effective in blocking inflammation-induced bone loss, they are less effective at rebuilding bone. We have previously shown that treatment with sclerostin antibody (Scl-AbI) builds bone and can prevent or restore bone loss in a murine model of inflammatory bowel disease. In this study, we tested the effect of Scl-AbI in a murine model of rheumatoid arthritis (the collagen-induced arthritis model, CIA). We hypothesised that sclerostin blockade can protect and restore bone both locally and systemically without affecting progression of inflammation.

Methods

CIA was induced in male DBA/1 mice, which were treated with either PBS or Scl-AbI (10 mg/kg, weekly) prophylactically for 55 days or therapeutically for 21 days (starting 14 days post onset of arthritis). Systemic inflammation was assessed by measuring the serum concentration of anti-CII IgG1, IgG2a and IgG2b by ELISA. Changes in bone mass and structure, either at sites remote from the joints or at periarticular sites, were measured using DEXA and microCT. Bone focal erosion was assessed in microCT scans of ankle and knee joints.

Results

Circulating anti-CII immunoglobulins were significantly elevated in mice with CIA and there were no significant differences in the levels of anti-CII immunoglobulins in mice treated with PBS or Scl-ABI. Prophylactic Scl-AbI treatment prevented the decrease in whole body bone mineral density (BMD) and in the bone volume fraction at axial (vertebral body) and appendicular (tibial proximal metaphysis trabecular and mid-diaphysis cortical bone) sites seen in PBS-treated CIA mice, but did not prevent the formation of focal bone erosions on the periarticular bone in the knee and ankle joints. In the therapeutic study, Scl-AbI restored BMD and bone volume fraction at all assessed sites but was unable to repair focal erosions.

Conclusions

Sclerostin blockade prevented or reversed the decrease in axial and appendicular bone mass in the murine model of rheumatoid arthritis, but did not affect systemic inflammation and was unable to prevent or repair local focal erosion.     

Effect of cell therapy with allogeneic osteoblasts on bone repair of rat calvaria defects

Background aims

Regenerative medicine strategies based on cell therapy are considered a promising approach to repair bone defects. The aims of this study were to evaluate the effect of subculturing on the osteogenic potential of osteoblasts derived from newborn rat calvaria and the effect of these osteoblasts on bone repair of rat calvaria defects.

Pseudofracture: An Acute Peripheral Tissue Trauma Model

Following trauma there is an early hyper-reactive inflammatory response that can lead to multiple organ dysfunction and high mortality in trauma patients; this response is often accompanied by a delayed immunosuppression that adds the clinical complications of infection and can also increase mortality.^1-9 Many studies have begun to assess these changes in the reactivity of the immune system following trauma.^10-15 Immunologic studies are greatly supported through the wide variety of transgenic and knockout mice available for in vivo modeling; these strains aid in detailed investigations to assess the molecular pathways involved in the immunologic responses.^16-21The challenge in experimental murine trauma modeling is long term investigation, as fracture fixation techniques in mice, can be complex and not easily reproducible.^22-30This pseudofracture model, an easily reproduced trauma model, overcomes these difficulties by immunologically mimicking an extremity fracture environment, while allowing freedom of movement in the animals and long term survival without the continual, prolonged use of anaesthesia. The intent is to recreate the features of long bone fracture; injured muscle and soft tissue are exposed to damaged bone and bone marrow without breaking the native bone.The pseudofracture model consists of two parts: a bilateral muscle crush injury to the hindlimbs, followed by injection of a bone solution into these injured muscles. The bone solution is prepared by harvesting the long bones from both hindlimbs of an age- and weight-matched syngeneic donor. These bones are then crushed and resuspended in phosphate buffered saline to create the bone solution.Bilateral femur fracture is a commonly used and well-established model of extremity trauma, and was the comparative model during the development of the pseudofracture model. Among the variety of available fracture models, we chose to use a closed method of fracture with soft tissue injury as our comparison to the pseudofracture, as we wanted a sterile yet proportionally severe peripheral tissue trauma model. ³¹Hemorrhagic shock is a common finding in the setting of severe trauma, and the global hypoperfusion adds a very relevant element to a trauma model. ^32-36 The pseudofracture model can be easily combined with a hemorrhagic shock model for a multiple trauma model of high severity. ³⁷Download video file.^{(62M, mov)}     

Estradiol ameliorates arthritis and protects against systemic bone loss in Staphylococcus aureus infection in mice

Introduction

Staphylococcus aureus is a common cause of bacterial arthritis, which is associated with progressive bone loss in affected joints. We recently showed that S. aureus infection also induces a significant systemic bone loss in mice. This study was performed to assess the effect of estradiol treatment on the clinical course and outcome of S. aureus arthritis and on infection-induced bone loss in experimental S. aureus infection.

Methods

Mice were ovariectomized, treated with estradiol or placebo, and S. aureus infection was established by intravenous inoculation of bacteria.

Results

Estradiol treatment was found to decrease significantly the frequency and clinical severity of S. aureus arthritis, a finding that was accompanied with significantly higher serum levels of interleukin-10 in estradiol-treated mice. Estradiol was also highly protective against S. aureus-induced systemic trabecular, and cortical bone loss. Lack of endogenous estrogens and S. aureus infection had additive effects on trabecular bone loss. The S. aureus-infected, ovariectomized mice lost as much as 76% of their trabecular bone mass.

Conclusions

Treatment with estradiol ameliorates S. aureus arthritis and is protective against infection-induced systemic bone loss in experimental S. aureus infection.     

Lyophilized allogeneic bone tissue as an antibiotic carrier

The rising number of primary joint replacements worldwide causes an increase of revision surgery of endoprostheses due bacterial infection. Revision surgery using non-cemented implants seems beneficial for the long-term outcome and the use of antibiotic-impregnated bone grafts might control the infection and give a good support for the implant. In this study we evaluated the release of antibiotics from fresh-frozen and lyophilized allogeneic bone grafts. Lyophilized bone chips and fresh frozen bone chips were mixed with gentamicin sulphate, gentamicin palmitate, vancomycin, calcium carbonate/calcium sulphate impregnated with gentamicin sulphate, and calcium carbonate/calcium sulphate bone substitute material impregnated with vancomycin. The efficacy of each preparation was measured by drug release tests and bacterial susceptibility using B. subtilis, S. aureus and methicillin-resistant Staphylococcus aureus. The release of gentamicin from lyophilized bone was similar to the release rate from fresh frozen bone during all the experimental time. That fact might be related to the similar porosity and microstructure of the bone chips. The release of gentamicin from lyophilized and fresh frozen bone was high in the first and second day, decreasing and keeping a low rate until the end of the second week. Depending on the surgical strategy either polymethylmethacrylate or allogeneic bone are able to deliver sufficient concentrations of gentamicin to achieve bacterial inhibition within two weeks after surgery. In case of uncemented revision of joint replacements allogeneic bone is able to deliver therapeutic doses of gentamicin and peak levels immediately after implantation during a fortnight. The use of lyophilized and fresh frozen bone allografts as antibiotic carriers is recommended for prophylaxis of bone infection.     

Reconstruction of Beagle Hemi-Mandibular Defects with Allogenic Mandibular Scaffolds and Autologous Mesenchymal Stem Cells

Objective

Massive bone allografts are frequently used in orthopedic reconstructive surgery, but carry a high failure rate of approximately 25%. We tested whether treatment of graft with mesenchymal stem cells (MSCs) can increase the integration of massive allografts (hemi-mandible) in a large animal model.

Methods

Thirty beagle dogs received surgical left-sided hemi-mandibular defects, and then divided into two equal groups. Bony defects of the control group were reconstructed using allografts only. Those of the experimental group were reconstructed using allogenic mandibular scaffold-loaded autologous MSCs. Beagles from each group were killed at4 (n = 4), 12 (n = 4), 24 (n = 4) or 48 weeks (n = 3) postoperatively. CT and micro-CT scans, histological analyses and the bone mineral density (BMD) of transplants were used to evaluate defect reconstruction outcomes.

Results

Gross and CT examinations showed that the autologous bone grafts had healed in both groups. At 48 weeks, the allogenic mandibular scaffolds of the experimental group had been completely replaced by new bone, which has a smaller surface area to that of the original allogenic scaffold, whereas the scaffold in control dogs remained the same size as the original allogenic scaffold throughout. At 12 weeks, the BMD of the experimental group was significantly higher than the control group (p<0.05), and all micro-architectural parameters were significantly different between groups (p<0.05). Histological analyses showed almost all transplanted allogeneic bone was replaced by new bone, principally fibrous ossification, in the experimental group, which differed from the control group where little new bone formed.

Conclusions

Our study demonstrated the feasibility of MSC-loaded allogenic mandibular scaffolds for the reconstruction of hemi-mandibular defects. Further studies are needed to test whether these results can be surpassed by the use of allogenic mandibular scaffolds loaded with a combination of MSCs and osteoinductive growth factors.     

Bone bank service in Odense, Denmark. Audit of the first ten years with bone banking at the Department of Orthopaedics, Odense University Hospital

There has been an increase in the demand for allograft bone in recentyears. The Odense University Hospital bone bank has been in function since1990,and this paper outlines our results during the 10 year period 1990–1999.Potential donors were screened by contemporary banking techniques which includea social history, donor serum tests for HIV, hepatitis B and C, and graftmicrobiology. The bones were stored at –80 °C. No typeofsecondary sterilisation was made. 423 femoral heads were approved and donatedto300 patients,1–6 heads/operation. The allografts have been used mainly toreconstruct defects at revision hip arthroplasty (34%), and for fracturesurgery(24%). 7 % of all transplanted patients were reoperated because of infection.Inthe hip revision group the infection rate was 4 %. There were no cases ofdisease transmission. During the 10 year period there was a change in theclinical use of the allografts. In the first years the allografts were mainlyused for spinal fusion surgery, but today the majority are used in hip revisionand fracture surgery. The clinical results correspond to those reported inlarger international series.     

Safety and efficacy of botox injection in alleviating post-operative pain and improving quality of life in lower extremity limb lengthening and deformity correction

Background

Distraction osteogenesis is the standard treatment for the management of lower limb length discrepancy of more than 3 cm and bone loss secondary to congenital anomalies, trauma or infection. This technique consists of an osteotomy of the bone to be lengthened, application of an external fixator, followed by gradual and controlled distraction of the bone ends. Although limb lengthening using the Ilizarov distraction osteogenesis principle yields excellent results in most cases, the technique has numerous problems and is not well tolerated by many children. The objective of the current study is to determine if Botulinum Toxin A (BTX-A), which is known to possess both analgesic and paralytic actions, can be used to alleviate post-operative pain and improve the functional outcome of children undergoing distraction osteogenesis.

Methods/Design

The study design consists of a multi centre, randomized, double-blinded, placebo-controlled trial. Patients between ages 5–21 years requiring limb lengthening or deformity correction using distraction will be recruited from 6 different sites (Shriners Hospital for Children in Montreal, Honolulu, Philadelphia and Portland as well as DuPont Hospital for Children in Wilmington, Delaware and Hospital for Sick Children in Toronto, Ont). Approximately 150 subjects will be recruited over 2 years and will be randomized to either receive 10 units per Kg of BTX-A or normal saline (control group) intraoperatively following the surgery. Functional outcome effects will be assessed using pain scores, medication dosages, range of motion, flexibility, strength, mobility function and quality of life of the patient. IRB approval was obtained from all sites and adverse reactions will be monitored vigorously and reported to IRB, FDA and Health Canada.

Discussion

BTX-A injection has been widely used world wide with no major side effects reported. However, to the best of our knowledge, this is the first time BTX-A is being used under the context of limb lengthening and deformity correction.

Trial Registration

NCT00412035     

A bone remodelling model coupling microdamage growth and repair by 3D BMU-activity

Bone as most of living tissues is able, during its entire lifetime, to adapt its internal microstructure and subsequently its associated mechanical properties to its specific mechanical and physiological environment in a process commonly known as bone remodelling. Bone is therefore continuously renewed and microdamage, accumulated by fatigue or creep, is removed minimizing the risk of fracture. Nevertheless, bone is not always able to repair itself completely. Actually, if bone repairing function is slower than microdamage accumulation, a type of bone fracture, usually known as stress fracture, can finally evolve. In this paper, we propose a bone remodelling continuous model able to simulate microdamage growth and repair in a coupled way and able therefore to predict the occurrence of stress fractures. The biological bone remodelling process is modelled in terms of equations that describe the activity of basic multicellular units. The predicted results show a good correspondence with experimental and clinical data. For example, in disuse, bone porosity increases until an equilibrium situation is achieved. In overloading, bone porosity decreases unless the damage rate is so high that causes resorption or stress fracture.Research partially supported by Diputación General de Aragón project P–008/2001) and National Network IM3 (Molecular and Multimodal Medical Imaging, Spanish Ministry of Health, Associated Partner, 300++, 2003-2005)     

Intra-articular knee implantation of autologous bone marrow–derived mesenchymal stromal cells in rheumatoid arthritis patients with knee involvement: Results of a randomized,triple-blind,placebo-controlled phase 1/2 clinical trial

Background

In this study, we intend to assess the safety and tolerability of intra-articular knee implantation of autologous bone marrow–derived mesenchymal stromal cells (MSCs) in patients with rheumatoid arthritis (RA) and to determine the preliminary clinical efficacy data in this population. The trial registration numbers are as follows: Royan Institute Ethics Committee: AC/91/1133; NCT01873625.

Bangkok Biomaterial Center: 15 Years Experience in Tissue Banking

Tissue banking is started in Thailand in 1979 at the Department of Orthopaedic Surgery, Siriraj Hospital, Bangkok. At that time tissues produced were freeze-dried bone allografts which were sterilized by ethylene oxide. In 1984, the freeze-dried tissue allograft project received an award from the National Research Council of Thailand. The Bangkok Biomaterial Center was officially inaugurated on December 6, 1984 under the Royal Patronage of H.R.H. Princess Galyanivadhana and is located inside the Siriraj Hospital. The Center is involved in the procurement, processing, storage and development of bone and tissue allografts. A variety of allografts including bone, cartilage, fascia lata, dura mater, cornea and also cardiovascular tissues have been procured and processed. Preservation and long-term storage are accomplished by freeze drying and deep freezing. Grafts prepared by the Center are supplied free of charge at the request of surgeons in hospitals throughout Thailand and in neighboring countries. The Center acts as the National Tissue and Allograft Bank of Thailand. From December 1984 to February 2000, the Center has processed a total of 20524 allografts: 16981 freeze-dried bones, 705 deep-frozen bones, 1838 freeze-dried amnion, 559 freeze-dried dura mater, 342 freeze-dried fascia lata, 46 costal cartilage, 18 corneas, 2 skin, 5 trachea, 22 fresh tendon and 6 bone substitutes. The allografts processed were used in 2049 patients by 223 surgeons in 53 hospitals in Thailand and 4 cases in neighboring countries. There have been 413 cadaveric donors, 619 living donors, 16 brain dead donors and 270 graveyard donors. There have been complications in 126 patients (6.14%) due to various clinical conditions. There have been production and application of 4 hydroxyapatite occular implant by the Center. The Center is in the process of establishing a full-fledged Research, Clinical and Cell Culture Laboratory.     

Restoration of the GM2 Ganglioside Metabolism in Bone Marrow–Derived Stromal Cells from Tay-Sachs Disease Animal Model

The therapeutic potential of bone marrow–derived stromal cells for the therapy of Tay-Sachs disease is primarily related to the restoration of their own GM2 ganglioside storage. With this aim, we produced bone marrow–derived stromal cells from the adult Tay-Sachs animal model and transduced them with a retroviral vector encoding for the -subunit of the lysosomal enzyme -hexosaminidase A (E.C. 3.2.1.52). Our results demonstrate that transduced Tay-Sachs bone marrow–derived stromal cells have -hexosaminidase A comparable to that of bone marrow-derived stromal cells from wild-type mice. Moreover, -hexosaminidase A in transduced Tay-Sachs bone marrow-derived stromal cells was able to hydrolyze the GM2 ganglioside in a feeding experiment, thus demonstrating the correction of the altered phenotype.     

The many facets of disseminated parenchymal brain cysticercosis: A differential diagnosis with important therapeutic implications

Neurocysticercosis (NCC), the infection of the nervous system by the cystic larvae of Taenia solium, is a highly pleomorphic disease because of differences in the number and anatomical location of lesions, the viability of parasites, and the severity of the host immune response. Most patients with parenchymal brain NCC present with few lesions and a relatively benign clinical course, but massive forms of parenchymal NCC can carry a poor prognosis if not well recognized and inappropriately managed. We present the main presentations of massive parenchymal NCC and their differential characteristics.

Infection of the central nervous system by the larval stage of Taenia solium—the pork tapeworm—causes neurocysticercosis (NCC), a highly pleomorphic disease [1]. This pleomorphism is partly related to differences in the number and anatomical location of lesions, the viability of parasites, and the severity of the host immune response against the infection. Cysticerci may be located within the brain parenchyma, the subarachnoid space, the ventricular system, the spinal cord, the sellar region, or even the subdural space.Most patients with parenchymal NCC present with few lesions and a clinical course that is often more benign than that observed in the subarachnoid and ventricular forms of NCC, where a sizable proportion of patients are left with disabling sequelae or may even die as a result of the disease [2,3]. Nevertheless, massive forms of parenchymal NCC require special attention to reduce the risk of complications related to the disease itself or to an inadequate treatment. Here, we present the main presentations of massive parenchymal NCC and their differential characteristics. There is no standardized definition of how many cysts constitute massive NCC. While the term “massive” has usually been applied when there are more than 100 lesions in the brain parenchyma, others have used smaller numbers (50), and there is not a defined cutoff.     

Controlled release of injectable liposomal in situ gel loaded with recombinant human bone morphogenetic protein-2 for the repair of alveolar bone clefts in rabbits

Background and objective: The aim of the present study was to develop and examine a new non-invasive injectable graft for the repair of alveolar bone clefts using recombinant human bone morphogenetic protein-2 (rhBMP-2) encapsulated within injectable liposomal in situ gel (LIG).

Method: Different liposomal formulations loaded with rhBMP-2 were prepared, and the effects of the preparation methods and lipid content on the efficiency of rhBMP-2 encapsulation within the liposomes were studied. For the preparation of in situ gel, deacetylated gellan gum (DGG) was used, and the in vitro gelation characteristics of the gel were evaluated. In vivo pharmacokinetics and histology were also assessed. Critical size alveolar defects were surgically created in the maxillae of 30 New Zealand rabbits and treated with different injectable formulae, including rhBMP-2 liposomes and in situ gel (rhBMP-2-LIG).

Results: The results indicated that the prepared rhBMP-2-LIG prolonged the release and residence time of BMP-2 within rabbits for more than 7 days. Histomorphometric assessment showed 67% trabecular bone filling of the defects treated using this novel formula.

Conclusion: BMP-2-LIG is a promising delivery device for the repair of alveolar bone defects associated with cleft deformities.     

Evaluation of bone healing following Er:YAG laser ablation in rat calvaria compared with bur drilling

The Er:YAG laser is currently used for bone ablation. However, the effect of Er:YAG laser irradiation on bone healing remains unclear. The aim of this study was to investigate bone healing following ablation by laser irradiation as compared with bur drilling. Rat calvarial bone was ablated using Er:YAG laser or bur with water coolant. Er:YAG laser effectively ablated bone without major thermal changes. In vivo micro‐computed tomography analysis revealed that laser irradiation showed significantly higher bone repair ratios than bur drilling. Scanning electron microscope analysis showed more fibrin deposition on laser‐ablated bone surfaces. Microarray analysis followed by gene set enrichment analysis revealed that IL6/JAK/STAT3 signaling and inflammatory response gene sets were enriched in bur‐drilled bone at 6 hours, whereas the E2F targets gene set was enriched in laser‐irradiated bone. Additionally, Hspa1a and Dmp1 expressions were increased and Sost expression was decreased in laser‐irradiated bone compared with bur‐drilled bone. In granulation tissue formed after laser ablation, Alpl and Gblap expressions increased compared to bur‐drilled site. Immunohistochemistry showed that osteocalcin‐positive area was increased in the laser‐ablated site. These results suggest that Er:YAG laser might accelerate early new bone formation with advantageous surface changes and cellular responses for wound healing, compared with bur‐drilling.      

Inside Front Cover: Near‐infrared bone densitometry: A feasibility study on distal radius measurement (J. Biophotonics 7/2018)

This study provides a simple method to detect human distal radius bone density based on near infrared (NIR) imaging. The information of bone mineral density can be measured by transluminational optical bone densitometric system. Compared to dual‐energy x‐ray absorptiometry (DXA) results in clinical trial, NIR images show a strong correlation to DXA. Further details can be found in the article by Chun Chung, Yu‐Pin Chen, Tsai‐Hsueh Leu, and Chia‐Wei Sun ( e201700342 ).

     

Analysis of DNA Double-strand Break (DSB) Repair in Mammalian Cells

DNA double-strand breaks are the most dangerous DNA lesions that may lead to massive loss of genetic information and cell death. Cells repair DSBs using two major pathways: nonhomologous end joining (NHEJ) and homologous recombination (HR). Perturbations of NHEJ and HR are often associated with premature aging and tumorigenesis, hence it is important to have a quantitative way of measuring each DSB repair pathway. Our laboratory has developed fluorescent reporter constructs that allow sensitive and quantitative measurement of NHEJ and HR. The constructs are based on an engineered GFP gene containing recognition sites for a rare-cutting I-SceI endonuclease for induction of DSBs. The starting constructs are GFP negative as the GFP gene is inactivated by an additional exon, or by mutations. Successful repair of the I-SceI-induced breaks by NHEJ or HR restores the functional GFP gene. The number of GFP positive cells counted by flow cytometry provides quantitative measure of NHEJ or HR efficiency.Download video file.^{(82M, mov)}     

The effects of different exercise modes for preventing endothelial dysfunction of arteries and bone loss in ovariectomized rats

[Purpose]

Several epidemiological studies have demonstrated that there are positive correlations between vascular disorders and bone loss in postmenopausal women. The aim of the present study was to examine the effect of different types of exercise (e.g., climbing and swimming) for preventing endothelial dysfunction of arteries and bone loss in ovariectomized rats.

[Methods]

Twenty Sprague-Dawley female rats were randomly divided into three groups: ovariectomy (OVX) plus treatment with vitamin D₃ and nicotine (VDN) (control rats [Con], n = 7), which is an animal model for endothelial dysfunction and bone loss; voluntary climbing resistance exercise with OVX plus VDN (climbing rats [Clim], n = 6), and swimming exercise with OVX plus VDN (swimming rats [Swim], n = 7). The period of exercise training was 8 weeks.

[Results]

The endothelin-1 (ET-1) protein levels were significantly lower in the Clim and Swim groups than in the Con. The endothelial nitric oxide synthase protein levels were significantly higher in the Swim group than in the Con, but they did not differ between the Clim and Con groups. The cortical bone mineral density in the tibia and breaking energy of the femur were significantly higher in the Clim group than in the Con, but this positive effect was not seen in the Swim group.

[Conclusion]

Voluntary climbing exercise decreased arterial ET-1 protein levels and prevented bone loss in a postmenopause-model rat combining OVX and VDN. Conversely, swimming suppressed endothelial dysfunction of the arteries but did not prevent bone loss. Thus, the type of exercise should be cautiously chosen for enhancing vascular function and bone status, especially in females after menopause.