Effect of Vitamin E Supplement on Bone Turnover Markers in Postmenopausal Osteopenic Women: A Double-Blind, Randomized, Placebo-Controlled Trial.

Vitamin E is a strong anti-oxidative stress agent that affects the bone remodeling process. This study evaluates the effect of mixed-tocopherol supplements on bone remodeling in postmenopausal osteopenic women. A double-blinded, randomized, placebo-controlled trial study was designed to measure the effect of mixed-tocopherol on the bone turnover marker after 12 weeks of supplementation. All 52 osteopenic postmenopausal women were enrolled and allocated into two groups. The intervention group received mixed-tocopherol 400 IU/day, while the control group received placebo tablets. Fifty-two participants completed 12 weeks of follow-up. Under an intention-to-treat analysis, vitamin E produced a significant difference in the mean bone resorption marker (serum C-terminal telopeptide of type I collagen (CTX)) compared with the placebo group (-0.003 ± 0.09 and 0.121 ± 0.15, respectively (p < 0.001)). In the placebo group, the CTX had increased by 35.3% at 12 weeks of supplementation versus baseline (p < 0.001), while, in the vitamin E group, there was no significant change of bone resorption marker (p < 0.898). In conclusion, vitamin E (mixed-tocopherol) supplementation in postmenopausal osteopenic women may have a preventive effect on bone loss through anti-resorptive activity.

Cartilage and Bone Destruction in Arthritis: Pathogenesis and Treatment Strategy: A Literature Review.

Arthritis is inflammation of the joints accompanied by osteochondral destruction. It can take many forms, including osteoarthritis, rheumatoid arthritis, and psoriatic arthritis. These diseases share one commonality-osteochondral destruction based on inflammation. The background includes a close interaction between osseous tissues and immune cells through various inflammatory cytokines. However, the tissues and cytokines that play major roles are different in each disease, and as a result, the mechanism of osteochondral destruction also differs. In recent years, there have been many findings regarding not only extracellular signaling pathways but also intracellular signaling pathways. In particular, we anticipate that the intracellular signals of osteoclasts, which play a central role in bone destruction, will become novel therapeutic targets. In this review, we have summarized the pathology of arthritis and the latest findings on the mechanism of osteochondral destruction, as well as present and future therapeutic strategies for these targets.

Electroacupuncture increases immunoexpression of CB1 and CB2 receptors in experimental model of inflammatory bone loss.

This study evaluated the participation of CB1 and CB2 receptors in the antiresorptive effect of electroacupuncture (EA) on an experimental model of inflammatory bone loss in rats. 30 rats were divided into five groups: C (control); EP (experimental periodontitis); EA (C+ EA); EP-EA (EP+ EA in the acupoints LI4, LG11, ST36, ST44); EP - EA-sham (EP+ EA in sham acupoints). For the EP groups, a ligature was placed around the right mandibular first molars at day 1. Sessions of EA or EA-sham were assigned every other day. Animals were euthanized at day 11. Histometric analysis was performed to evaluate the percentage of bone area in the furcation area. Immunolabeling patterns in the periodontal tissues and immunofluorescent staining in the trigeminal ganglia and in the trigeminal spinal tract for CB1 and CB2 receptors were performed. It was observed increased bone loss in the furcation in the EP and EP-EA-sham groups, in comparison to the other groups (p < 0.05). Enhanced CB2 immunolabeling was observed in the periodontal tissues in the EP-EA group, when compared to the EP and EP-EA-sham groups (p < 0.05). Increased CB1 immunofluorescent staining was observed in the neural tissues in the EA treated group in comparison with the other groups (p < 0.05), while no expression of CB2 was observed in those regions. Our study showed that in the presence of inflammatory bone disease, EA treatment reduced bone erosion and increased the immunoexpression of CB1 in the neural tissues and CB2 in the periodontal tissues.

Common mechanisms and holistic care in atherosclerosis and osteoporosis.

Cardiovascular (CV) disease and osteoporosis (OP) have become increasing challenges in the aging population and even more in patients with inflammatory rheumatic diseases, such as rheumatoid arthritis, spondyloarthropathies, and systemic lupus erythematosus. In this review, we discuss how the epidemiology and pathogenesis of CV events and OP are overlapping. Smoking, diabetes mellitus, physical inactivity as conventional risk factors as well as systemic inflammation are among the modifiable risk factors for both CV events and bone loss. In rheumatic patients, systemic "high-grade" inflammation may be the primary driver of accelerated atherogenesis and bone resorption. In the general population, in which some individuals might have low-grade systemic inflammation, a holistic approach to drug treatment and lifestyle modifications may have beneficial effects on the bone as well as the vasculature. In rheumatic patients with accelerated inflammatory atherosclerosis and bone loss, the rapid and effective suppression of inflammation in a treat-to-target regime, aiming at clinical remission, is necessary to effectively control comorbidities.

Mechanical Loading Attenuates Radiation-Induced Bone Loss in Bone Marrow Transplanted Mice.

Exposure of bone to ionizing radiation, as occurs during radiotherapy for some localized malignancies and blood or bone marrow cancers, as well as during space travel, incites dose-dependent bone morbidity and increased fracture risk. Rapid trabecular and endosteal bone loss reflects acutely increased osteoclastic resorption as well as decreased bone formation due to depletion of osteoprogenitors. Because of this dysregulation of bone turnover, bone's capacity to respond to a mechanical loading stimulus in the aftermath of irradiation is unknown. We employed a mouse model of total body irradiation and bone marrow transplantation simulating treatment of hematologic cancers, hypothesizing that compression loading would attenuate bone loss. Furthermore, we hypothesized that loading would upregulate donor cell presence in loaded tibias due to increased engraftment and proliferation. We lethally irradiated 16 female C57Bl/6J mice at age 16 wks with 10.75 Gy, then IV-injected 20 million GFP(+) total bone marrow cells. That same day, we initiated 3 wks compression loading (1200 cycles 5x/wk, 10 N) in the right tibia of 10 of these mice while 6 mice were irradiated, non-mechanically-loaded controls. As anticipated, before-and-after microCT scans demonstrated loss of trabecular bone (-48.2% Tb.BV/TV) and cortical thickness (-8.3%) at 3 wks following irradiation. However, loaded bones lost 31% less Tb.BV/TV and 8% less cortical thickness (both p<0.001). Loaded bones also had significant increases in trabecular thickness and tissue mineral densities from baseline. Mechanical loading did not affect donor cell engraftment. Importantly, these results demonstrate that both cortical and trabecular bone exposed to high-dose therapeutic radiation remain capable of an anabolic response to mechanical loading. These findings inform our management of bone health in cases of radiation exposure.

Pharmacological and biological therapeutic strategies for osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a connective tissue disorder characterized by bone fragility, low bone mass, and bone deformities. The majority of cases are caused by autosomal dominant pathogenic variants in the COL1A1 and COL1A2 genes that encode type I collagen, the major component of the bone matrix. The remaining cases are caused by autosomal recessively or dominantly inherited mutations in genes that are involved in the post-translational modification of type I collagen, act as type I collagen chaperones, or are members of the signaling pathways that regulate bone homeostasis. The main goals of treatment in OI are to decrease fracture incidence, relieve bone pain, and promote mobility and growth. This requires a multi-disciplinary approach, utilizing pharmacological interventions, physical therapy, orthopedic surgery, and monitoring nutrition with appropriate calcium and vitamin D supplementation. Bisphosphonate therapy, which has become the mainstay of treatment in OI, has proven beneficial in increasing bone mass, and to some extent reducing fracture risk. However, the response to treatment is not as robust as is seen in osteoporosis, and it seems less effective in certain types of OI, and in adult OI patients as compared to most pediatric cases. New pharmacological treatments are currently being developed, including anti-resorptive agents, anabolic treatment, and gene- and cell-therapy approaches. These therapies are under different stages of investigation from the bench-side, to pre-clinical and clinical trials. In this review, we will summarize the recent findings regarding the pharmacological and biological strategies for the treatment of patients with OI. © 2016 Wiley Periodicals, Inc.

Sinusoidal electromagnetic fields promote bone formation and inhibit bone resorption in rat femoral tissues in vitro.

Effects of sinusoidal electromagnetic fields (SEMFs) on bone metabolism have not yet been well defined. The present study investigated SEMF effects on bone formation and resorption in rat femur bone tissues in vitro. Cultured femur diaphyseal (cortical bone) and metaphyseal (trabecular bone) tissues were treated with 50 Hz 1.8 mT SEMFs 1.5 h per day for up to 12 days and treatment effects on bone formation and resorption markers and associated gene expression were examined. Treatment with SEMFs caused a significant increase in alkaline phosphatase (ALP) activity and inhibited the tartrate-resistant acid phosphatase (TRACP) activity in the femoral diaphyseal or metaphyseal tissues. SEMFs also significantly increased levels of mRNA expression of osterix (OSX), insulin-like growth factor (IGF-1) and ALP in the bone tissues. SEMF treatment decreased glucose content and increased lactic acid contents in the culture conditioned medium. In addition, treatment with SEMFs decreased mRNA expression levels of bone resorption-related genes TRACP, macrophage colony stimulating factor (M-CSF) and cathepsin K (CTSK) in the cultured bone tissues. In conclusion, the current study demonstrated that treatment with 1.8 mT SEMFs at 1.5 h per day promoted bone formation, increased metabolism and inhibited resorption in both metaphyseal and diaphyseal bone tissues in vitro.

Animal Models of Bone Loss in Inflammatory Arthritis: from Cytokines in the Bench to Novel Treatments for Bone Loss in the Bedside-a Comprehensive Review.

Throughout life, bone is continuously remodelled. Bone is formed by osteoblasts, from mesenchymal origin, while osteoclasts induce bone resorption. This process is tightly regulated. During inflammation, several growth factors and cytokines are increased inducing osteoclast differentiation and activation, and chronic inflammation is a condition that initiates systemic bone loss. Rheumatoid arthritis (RA) is a chronic inflammatory auto-immune disease that is characterised by active synovitis and is associated with early peri-articular bone loss. Peri-articular bone loss precedes focal bone erosions, which may progress to bone destruction and disability. The incidence of generalised osteoporosis is associated with the severity of arthritis in RA and increased osteoporotic vertebral and hip fracture risk. In this review, we will give an overview of different animal models of inflammatory arthritis related to RA with focus on bone erosion and involvement of pro-inflammatory cytokines. In addition, a humanised endochondral ossification model will be discussed, which can be used in a translational approach to answer osteoimmunological questions.

Low iron status as a factor of increased bone resorption and effects of an iron and vitamin D-fortified skimmed milk on bone remodelling in young Spanish women.

PURPOSE: This study aimed to determine whether there is a relationship between iron status and bone metabolism, and to compare the effects of the consumption, as part of the usual diet, of an iron or iron and vitamin D-fortified skimmed milk on bone remodelling in iron-deficient women. METHODS: Young healthy iron-deficient or iron-sufficient women (serum ferritin ≤30 ng/mL or >30 ng/mL, respectively) were recruited. Iron-deficient women were assigned to a nutritional intervention consisting of a randomised, controlled, double-blind, parallel design trial of 16 weeks during winter. They consumed, as part of their usual diet, an iron (Fe group, n = 54) or iron and vitamin D-fortified (Fe+D group, n = 55) flavoured skimmed milk (iron, 15 mg/day; vitamin D3, 5 µg/day, 200 IU). The iron-sufficient women followed their usual diet without supplementation (R group, n = 56). Dietary intake, body weight, iron biomarkers, 25-hydroxyvitamin D (25OHD), parathyroid hormone (PTH), procollagen-type 1 N-terminal propeptide (P1NP), and aminoterminal telopeptide of collagen I (NTx) were determined. RESULTS: Negative correlations were found between baseline log-ferritin and log-NTx (p < 0.001), and between transferrin and P1NP (p = 0.002). Serum 25OHD increased (from 62 ± 21 to 71 ± 21 nmol/L, mean ± SD, p < 0.001) while P1NP and NTx decreased in Fe+D during the assay (p = 0.004 and p < 0.001, respectively). NTx was lower in Fe+D compared to Fe at week 8 (p < 0.05) and was higher in Fe and Fe+D compared to R throughout the assay (p < 0.01). PTH did not show changes. CONCLUSIONS: Iron deficiency is related with higher bone resorption in young women. Consumption of a dairy product that supplies 5 µg/day of vitamin D3 reduces bone turnover and increases circulating 25OHD to nearly reach an optimal vitamin D status, defined as 25OHD over 75 nmol/L.

Hyperbaric oxygen stimulates vascularization and bone formation in rat calvarial defects.

Hyperbaric oxygen (HBO) therapy is used to treat or prevent tissue necrosis in patients undergoing irradiation. Many such patients require reconstructive surgery, but little is known of the effects of HBO on bone vascularization and regeneration. In this study, copolymer poly(l-lactide-co-1,5-dioxepan-2-one) (poly(LLA-co-DXO)) scaffolds were implanted into critical-sized calvarial defects in Wistar rats. The animals were randomly allotted to hyperbaric or normobaric oxygen groups. The treatment group received five sessions weekly for 90 min at increased atmospheric pressure, for up to 4 weeks. Samples were retrieved at weeks 2 and 8, i.e. after a total of 10 and 20 sessions, respectively. The samples were analyzed by real-time reverse transcriptase polymerase chain reaction (RT-PCR) and histology at week 2, and radiographically and histologically at week 8. At week 2, defects treated with HBO exhibited greater numbers of cells positive for the endothelial marker CD31, up-regulated gene expression of osteogenic markers, and down-regulated expression of pro-inflammatory cytokines. At week 8, radiographic examination revealed that calvarial defects subjected to HBO exhibited a higher percentage of radiopacities than normobaric controls, and histological examination disclosed enhanced bone healing. These results confirmed that HBO treatment was effective in stimulating vascularization and bone formation in rat calvarial defects.

Hungry bone syndrome: still a challenge in the post-operative management of primary hyperparathyroidism: a systematic review of the literature.

Hungry bone syndrome (HBS) refers to the rapid, profound, and prolonged hypocalcaemia associated with hypophosphataemia and hypomagnesaemia, and is exacerbated by suppressed parathyroid hormone (PTH) levels, which follows parathyroidectomy in patients with severe primary hyperparathyroidism (PHPT) and preoperative high bone turnover. It is a relatively uncommon, but serious adverse effect of parathyroidectomy. We conducted a literature search of all available studies reporting a 'hungry bone syndrome' in patients who had a parathyroidectomy for PHPT, to identify patients at risk and address the pitfalls in their management. The severe hypocalcaemia is believed to be due to increased influx of calcium into bone, due to the sudden removal of the effect of high circulating levels of PTH on osteoclastic resorption, leading to a decrease in the activation frequency of new remodelling sites and to a decrease in remodelling space, although there is no good documentation for this. Various risk factors have been suggested for the development of HBS, including older age, weight/volume of the resected parathyroid glands, radiological evidence of bone disease and vitamin D deficiency. The syndrome is reported in 25-90% of patients with radiological evidence of hyperparathyroid bone disease vs only 0-6% of patients without skeletal involvement. There is insufficient data-based evidence on the best means to treat, minimise or prevent this severe complication of parathyroidectomy. Treatment is aimed at replenishing the severe calcium deficit by using high doses of calcium supplemented by high doses of active metabolites of vitamin D. Adequate correction of magnesium deficiency and normalisation of bone turnover are required for resolution of the hypocalcaemia which may last for a number of months after successful surgery. Preoperative treatment with bisphosphonates has been suggested to reduce post-operative hypocalcaemia, but there are to date no prospective studies addressing this issue.

Bone remodeling and calcium homeostasis in patients with spinal cord injury: a review.

Patients with spinal cord injury exhibit early and acute bone loss with the major functional consequence being a high incidence of pathological fractures. The bone status of these patients is generally investigated by dual-energy x-ray absorptiometry, but this technique does not reveal the pathophysiological mechanism underlying the bone loss. Bone cell activity can be indirectly evaluated by noninvasive techniques, including measurement of specific biochemical markers of bone formation (such as osteocalcin or bone-alkaline phosphatase) and resorption (such as procollagen type I N- or C-terminal propeptide). The bone loss in spinal cord injury is clearly due to an uncoupling of bone remodeling in favor of bone resorption, which starts just after the injury and peaks at about 1 to 4 months. Beyond 6 months, bone resorption activity decreases progressively but remains elevated for many years after injury. Conversely, bone formation is less affected. Antiresorptive treatment induces an early and acute reduction in bone resorption markers. Level of injury and health-related complications do not seem to be implicated in the intensity of bone resorption. During the acute phase, the hypercalcemic status is associated with the suppression of parathyroid hormone and vitamin D metabolites. The high sensitivity of these markers after treatment suggests that they can be used for monitoring treatment efficacy and patient compliance. The concomitant use of bone markers and dual-energy x-ray absorptiometry may improve the physician's ability to detect patients at risk of severe bone loss and subsequent fractures.

Bone health issues in women with early-stage breast cancer receiving aromatase inhibitors.

Bone health is an important issue for women with all stages of breast cancer, but especially those with early-stage breast cancer receiving aromatase inhibitors (AIs). AIs have been shown to reduce bone mineral density and are associated with an increased incidence of fractures. Although AIs significantly improve survival times in early-stage breast cancer patients, many of these patients eventually develop metastatic bone disease. Therefore, identifying effective strategies for preventing bone metastases is needed. Results of preclinical studies with bisphosphonates show increased tumor cell kill in several breast cancer cell lines, but study results evaluating this class of drugs for prevention of bone metastases in women with early-stage breast cancer receiving adjuvant therapies have been inconsistent. However, several large studies to clarify the role of bisphosphonates in maintaining or improving bone health in these women are under way.

Seasonal variation of serum alpha- and beta-cryptoxanthin and 25-OH-vitamin D(3) in women with osteoporosis.

UNLABELLED: beta-Cryptoxanthin displays a unique anabolic effect on bone calcification. In women with osteoporosis, serum beta-cryptoxanthin and 25-OH-vitamin D(3) showed a weak but significant correlation and exhibited a complementary seasonal distribution. The potential role of beta-cryptoxanthin as a nutritional approach to improving bone health deserves further evaluation. INTRODUCTION: Dietary intake and serum levels of beta-cryptoxanthin have been inversely related to different bone and joint disorders and in vitro and animal studies have shown that beta-cryptoxanthin displays a unique anabolic effect on bone calcification. Due to the emerging role of beta-cryptoxanthin in bone biology, we aimed to assess the serum distribution and variability of beta-cryptoxanthin and their potential relation to 25-OH-vitamin D(3) in women with osteoporosis. METHODS: Serum concentrations of alpha- and beta-cryptoxanthin and 25-OH- D(3) in women with osteoporosis (N = 644) were analyzed using a quality-controlled high-performance liquid chromatography (HPLC) method. RESULTS: Overall, significant seasonal variations were found for the three analytes and inter-individual variation was also high (60-73%). beta-cryptoxanthin and 25-OH-vitamin D(3) exhibited a marked complementary seasonal distribution in serum, with vitamin D displaying the highest values in summer and beta-cryptoxanthin in winter. CONCLUSIONS: Given the anabolic effect of beta-cryptoxanthin on bone calcification and its complementary seasonal distribution with respect to 25-OH-vitamin D(3), the potential role of beta-cryptoxanthin as a sustainable nutritional approach to improving bone health deserves to be further evaluated.

GMP-grade preparation of biomimetic scaffolds with osteo-differentiated autologous mesenchymal stromal cells for the treatment of alveolar bone resorption in periodontal disease.

BACKGROUND: Periodontal disease is a degenerative illness that leads to resorption of the alveolar bone. Mesenchymal stromal cells (MSC) represent a novel tool for the production of biologic constructs for the treatment of degenerative bone diseases. The preparation of MSC differentiated into osteogenic lineage for clinical use requires the fulfillment of strict good manufacturing practice (GMP) procedures. METHODS: MSC were isolated from BM samples and then cultured under GMP conditions. MSC were characterized phenotypically and for their differentiative potential. Cells were seeded onto collagen scaffolds (Gingistat) and induced to differentiate into osteogenic lineages using clinical grade drugs compared with standard osteogenic supplements. Alizarin Red S stain was used to test the deposition of the mineral matrix. Standard microbiologic analysis was performed to verify the product sterility. RESULTS: The resulting MSC were negative for CD33, CD34 and HLA-DR but showed high expression of CD90, CD105 and HLA-ABC (average expressions of 94.3%, 75.8% and 94.2%, respectively). Chondrogenic, osteogenic and adipogenic differentiation potential was demonstrated. The MSC retained their ability to differentiate into osteogenic lineage when seeded onto collagen scaffolds after exposure to a clinical grade medium. Cell numbers and cell viability were adequate for clinical use, and microbiologic assays demonstrated the absence of any contamination. DISCUSSION: In the specific context of a degenerative bone disease with limited involvement of skeletal tissue, the combined use of MSC, exposed to an osteogenic clinical grade medium, and biomimetic biodegradable scaffolds offers the possibility of producing adequate numbers of biologic tissue-engineered cell-based constructs for use in clinical trials.

Regeneración ósea guiada utilizando membrana de óxido de aluminio en combinación con implantes oseointegrados / Guided bone regeneration using aluminum oxide membrane in combination with osseointegrated implants

La reabsorción ósea de los maxilares ha sido una de las mayorescomplicaciones al momento de rehabilitar a pacientes con implantes oseointegrados. El siguiente estudio evaluó la efectividad de la membrana de óxido de aluminio (alúmina), en la regeneración ósea de rebordes colapsados y alvéolos en los que se colocaron implantes. De un total de cinco pacientes seleccionados, se estudiaron siete sitios de los cuales tres correspondieron a un solo paciente. En cada sitio (alvéolo o reborde colapsado) se colocó un implante de titanio del sistema HIS y una membrana no biodegradable de óxido de aluminio (Allumina(R)), la cual fue retirada a las 14semanas. Todos los pacientes fueron sometidos al mismo procedimiento quirúrgico. La ganancia promedio en mm obtenidos en orden decreciente fue la siguiente: ANM: 1.7 mm, ANME: 1.6 mm, AND: 1.1 mm, AV: 1.0mm, AP: 0.5mm. Los resultados radiográficos ratificaron los resultados clínicosen cuanto a neoformación ósea, observándose además una favorable densidad ó se a periimplantaria. El análisis estadístico (basado en los resultados clínicos) t-student fue significativo para todos los parámetros evaluadoscon excepción de AP (AU)

Alveolar bone loss has been a very important cause ofcomplications in osseointegrated implant rehabilitation of edentulouspatients. This paper evaluates the effectiveness of aluminum oxidemembrane (Allumina) in the collapsed alveolar ridge where implantswere used. Seven sites were studied in 5 patients. In each of thesesites a HIS implant plus a non-biodegradable oxide aluminummembrane (Allumina®), was placed for 14 weeks. All patients weretreated with the same surgical protocol. The average gain (in mm)obtained in decreasing order was as follows: ANM: 1.7 mm, ANME:1.6 mm, AND: 1.1mm, AV: 1.0mm, AP: 0.5mm. The clinical resultswere radiographically verified and these showed bone neoformation,in addition to favorable peri-implant bone density. The t-Studentstatistical analysis based on the clinical results was significant forall the parameters evaluated with the exception of AP (AU)

ENA Actimineral Resource A restores bone loss and bone quality in ovariectomized rats.

The purpose of this study was to examine the effects of ENA Actimineral Resource A (ENA-A), seaweed origin alkaline water, on postmenopausal osteoporosis in ovariectomized (OVX) rats. The 12-week old Wistar rats were divided randomly into 4 groups: ovariectomized (OVX), OVX plus 0.5% ENA-A, OVX plus 5% ENA-A and OVX plus 10% ENA-A. A histopathological analysis indicated that ENA-A could prevent OVX-induced bone loss by increasing femur trabecular bone area in a dose-dependent manner. ENA-A significantly (p<0.05) increased serum estradiol levels, decreased serum osteocalcin activity and suppressed serum pyridinoline (PYD) levels. The in vitro effects of ENA-A were also studied using MC3T3-E1 cells. ENA-A significantly stimulated cell proliferation and increased both ALP activity and calcium deposition in a dose-dependent manner. These results suggest that the treatment of ovariectomized rats with ENA-A not only prevents bone resorption but also appears to maintain the cancellous bone structure of postmenopausal osteoporosis.

Anti-RANKL therapy for inflammatory bone disorders: Mechanisms and potential clinical applications.

Focal bone loss around inflamed joints in patients with autoimmune disease, such as rheumatoid arthritis, remains a serious clinical problem. The recent elucidation of the RANK/RANK-ligand/OPG pathway and its role as the final effector of osteoclastogenesis and bone resorption has brought a tremendous understanding of the pathophysiology of inflammatory bone loss, and has heightened expectation of a novel intervention. Here, we review the etiology of inflammatory bone loss, the RANK/RANK-ligand/OPG pathway, and the clinical development of anti-RANK-ligand therapy.

[Results of long term general therapy on experimental bone resorption in golden hamster]. / Résultats d'une thérapeutique générale á long terme (1) sur les résorptions osseuses expérimentales chez le Hamster doré

A restoring osteogenesis of osteoclastic lesions induced by the high carbohydrate Keyes diet, was brought about, at the alveolar bone level, with long term general therapy without any local treatment.