Dietary recommendations in the prevention and treatment of osteoporosis.

INTRODUCTION: This article presents the initial recommendations of the French Rheumatology Society (Société Française de Rhumatologie - SFR) and the Osteoporosis Research and Information Group (Groupe de Recherche et d'Informations sur les Ostéoporoses - GRIO) on the role of diet in the prevention and treatment of osteoporosis. METHODS: The recommendations were produced by a working group composed of rheumatologists, physician nutrition specialists and a geriatrician. Fifteen (15) questions pertaining to "daily practices" were preselected by the working group. For the literature review, the working group focussed mainly on the effects of diet on bone mineral density (BMD) and fractures, and primarily on meta-analyses of longitudinal studies and dietary intervention studies. RESULTS: A Mediterranean-type diet and the daily consumption of 2 to 3 dairy products are recommended. Together, these provide the calcium and "high quality" protein required to maintain a normal calcium-phosphorus balance and bone metabolism, and are associated with lower fracture risk. Conversely, unbalanced Western diets, vegan diets, weight-loss diets in non-overweight individuals, alcohol consumption and daily consumption of sodas are advised against. In terms of the beneficial effects on bone mineral density and fracture risk, current scientific data are either insufficient or too divergent to recommend increasing or restricting the consumption of tea or coffee, vitamins other than vitamin D, vitamin D-enriched or phytoestrogen-rich foods, calcium-enriched plant-based beverages, oral nutritional supplements, or dietary sources of prebiotics and probiotics. CONCLUSIONS: These are the first set of recommendations addressing the role of diet in the prevention and treatment of osteoporosis. More research is necessary to direct and support guidelines.

Lipid accumulation and mitochondrial abnormalities are associated with fiber atrophy in the skeletal muscle of rats with collagen-induced arthritis.

Rheumatoid arthritis (RA) has a negative impact on muscle mass, and reduces patient's mobility and autonomy. Furthermore, RA is associated with metabolic comorbidities, notably in lipid homeostasis by unknown mechanisms. To understand the links between the loss in muscle mass and the metabolic abnormalities, arthritis was induced in male Sprague Dawley rats (n = 11) using the collagen-induced arthritis model. Rats immunized with bovine type II collagen were compared to a control group of animals (n = 11) injected with acetic acid and complete Freund's adjuvant. The clinical severity of the ensuing arthritis was evaluated weekly by a semi-quantitative score. Skeletal muscles from the hind limb were used for the histological analysis and exploration of mitochondrial activity, lipid accumulation, metabolism and regenerative capacities. A significant atrophy in tibialis anterior muscle fibers was observed in the arthritic rats despite a non-significant decrease in the weight of the muscles. Despite moderate inflammation, accumulation of triglycerides (P < 0.05), reduced mitochondrial DNA copy number (P < 0.05) and non-significant dysfunction in mitochondrial cytochrome c oxidase activity were found in the gastrocnemius muscle. Concomitantly, our results suggested an activation of the muscle specific E3 ubiquitin ligases MuRF-1 and MAFbx. Finally, the adipose tissue from the arthritic rats exhibited decreased PPARγ mRNA suggesting reduced adipogenic capacities. In conclusion, the reduced adipose tissue adipogenic capacity and skeletal muscle mitochondrial capacity are probably involved in the activation of protein catabolism, inhibition of myogenesis, accumulation of lipids and fiber atrophy in the skeletal muscle during RA.

Tackling the question of micronutrients intake as one of the main levers in terms of Inuit food security.

PURPOSE OF REVIEW: The Inuit population living in North Canada is facing a drastic change in lifestyle, which has brought about a dramatic nutrition transition characterized by a decrease in the traditional foods consumption and an increasing reliance on processed, store-bought foods. This rapid dietary shift leads to a significant public health concern, as wild-harvested country foods are rich in many micronutrients including vitamins, trace elements and minerals while the most frequently eaten Western foods mainly provide energy, fat, carbohydrates and sodium. This review addresses the emerging strategies to tackle food insecurity in this population. RECENT FINDINGS: Recent studies indicate that diets with a higher fraction of traditional foods (and a lower fraction of ultra-processed foods) exhibit a better Healthy Eating Index. This provides a basis to develop new dietary policies anchored in contemporary food realities. SUMMARY: In Northern remote communities, improving food security requires holistic approaches. A mixed strategy that targets the revitalization of traditional foods systems and local food production initiatives seems the most promising strategy, to meet the dietary needs in terms of micronutrients, with respect to the cultural identity of local populations.

The effects of dietary fatty acids on bone, hematopoietic marrow and marrow adipose tissue in a murine model of senile osteoporosis.

Purpose: Marrow adipose tissue (MAT) expansion and associated lipotoxicity are important drivers of age-related bone loss and hematopoietic bone marrow (HBM) atrophy. Fish oil and borage oil (rich in ω3 fatty acids) can partially prevent aged-related bone loss in SAMP8 mice. However, whether preservation of bone mass in this progeria model is associated with MAT volumes remains unknown.Results: MAT volume fraction (MAT%) showed a negative association with hematopoietic bone marrow (HBM%;r=-0.836, p<0.001) and bone (bone%;r=-0.344, p=0.013) volume fractions.Adjusting for multiple comparisons, bone% was higher and MAT% was lower in Fish oil (FO)-supplemented groups vs. controls (p<0.001). HBM% did not differ significantly between the four groups. However, in the group supplemented with FO, HBM comprised higher fractions and MAT constituted lower fractions of total marrow vs. controls (p<0.001).Conclusion: Feeding FO-enriched diet prevented age-related bone and HBM loss, by reducing MAT expansion. Our results further emphasize on the role(s) of MAT expansion in bone and HBM atrophy.Methods: SAMP8 mice (n>9 /group) were allocated into 4 categories and fed a control ration, FO-, sunflower oil (SFO)- and borage oil-enriched diets for lifetime. Femurs were scanned using microcomputed tomography (µCT) and bone, MAT, and HBM volumes were determined using an image analysis software.

Impact of Eccentric or Concentric Training on Body Composition and Energy Expenditure.

PURPOSE: To compare the effects of 8-wk eccentric (ECC) versus concentric (CON) training using downhill and uphill running in rats on whole body composition, bone mineral density (BMD), and energy expenditure. METHODS: Animals were randomly assigned to one of the following groups: 1) control (CTRL), 2) +15% uphill-running slope (CON), 3) -15% downhill-running slope (ECC15), and 4) -30% downhill-running slope (ECC30). Those programs enabled to achieve conditions of isopower output for CON and ECC15 and of iso-oxygen uptake (V˙O2) for CON and ECC30. Trained rats ran 45 min at 15 m·min five times per week. Total body mass, fat body mass, and lean body mass (LBM) measured through EchoMRI™, and 24-h energy expenditure including basal metabolic rate (BMR) assessed using PhenoMaster/LabMaster™ cage system were obtained before and after training. At sacrifice, the right femur was collected for bone parameters analysis. RESULTS: Although total body mass increased in all groups over the 8-wk period, almost no change occurred for fat body mass in exercised groups (CON, -4.8 ± 6.18 g; ECC15, 0.6 ± 3.32 g; ECC30, 2.6 ± 6.01 g). The gain in LBM was mainly seen for ECC15 (88.9 ± 6.85 g) and ECC30 (101.6 ± 11.07 g). ECC was also seen to positively affect BMD. An increase in BMR from baseline was seen in exercise groups (CON, 13.9 ± 4.13 kJ·d; ECC15, 11.6 ± 5.10 kJ·d; ECC30, 18.3 ± 4.33 kJ·d) but not in CTRL one. This difference disappeared when BMR was normalized for LBM. CONCLUSIONS: Results indicate that for iso-V˙O2 training, the impact on LBM and BMD is enhanced with ECC as compared with CON, and that for isopower but lower V˙O2 ECC, an important stimulus for adaptation is still observed. This provides further insights for the use of ECC in populations with cardiorespiratory exercise limitations.

Biological effect of hydrolyzed collagen on bone metabolism.

Osteoporosis is a chronic and asymptomatic disease characterized by low bone mass and skeletal microarchitectural deterioration, increased risk of fracture, and associated comorbidities most prevalent in the elderly. Due to an increasingly aging population, osteoporosis has become a major health issue requiring innovative disease management. Proteins are important for bone by providing building blocks and by exerting specific regulatory function. This is why adequate protein intake plays a considerable role in both bone development and bone maintenance. More specifically, since an increase in the overall metabolism of collagen can lead to severe dysfunctions and a more fragile bone matrix and because orally administered collagen can be digested in the gut, cross the intestinal barrier, enter the circulation, and become available for metabolic processes in the target tissues, one may speculate that a collagen-enriched diet provides benefits for the skeleton. Collagen-derived products such as gelatin or hydrolyzed collagen (HC) are well acknowledged for their safety from a nutritional point of view; however, what is their impact on bone biology? In this manuscript, we critically review the evidence from literature for an effect of HC on bone tissues in order to determine whether HC may represent a relevant alternative in the design of future nutritional approaches to manage osteoporosis prevention.

GPR40 mediates potential positive effects of a saturated fatty acid enriched diet on bone.

SCOPE: The stimulation of the free fatty acid receptor G-protein coupled receptor (GPR) 40 by GW9508 prevents bone loss by inhibiting osteoclast activity, both in vitro and in vivo. Here, we questioned whether the stimulation of the GPR40 receptor by dietary fatty acids may lead to the same beneficial effect on bone. METHODS AND RESULTS: We investigated (i) the impact of a fatty acid enriched diet (high-fat diet [HFD]) on bone health in C57/BL6 female mice depending on (ii) the estrogen status (ovariectomy) and (iii) the genotype (GPR40+/+ or GPR40-/- ). Bone mineral density (BMD), body composition, weight, inflammation and bone remodeling parameters were monitored. HFD decreased BMD in HFD-SH-GPR40+/+ mice but OVX failed to further impact BMD in HFD-OVX-GPR40+/+ mice, while additional bone loss was observed in HFD-OVX-GPR40-/- animals. These data suggest that when stimulated by fatty acid enriched diets GPR40 contributes to counteract ovariectomy-induced bone alteration. The sparing effect is supported by the modulation of both the osteoprotegerin/receptor activator of nuclear factor kappa-B ligand (OPG/RANKL) ratio in blood stream and the expression level of inflammatory markers in adipose tissues. Bone preservation by GPR40 stimulation is dependent on the presence of long-chain saturated fatty acids. CONCLUSION: GPR40 contributes to counter ovariectomy-induced bone loss in a context of saturated fatty acid enrichment.

Berries, their micronutrients and bone health.

PURPOSE OF REVIEW: The design and the development of functional foods is a key issue for bone health and a scientific challenge as well. As most studies have focused on calcium, and have paid less attention to other nutrients, our knowledge of the influence of nutrition on bone health remains limited. It has been well acknowledged that the human diet contains a wide and complex range of bioactive molecules endowed with interesting protective properties. In this context, and according to their high content in micronutrients, a growing body of evidence has enlightened the high nutritional value of berries. This review addresses the emerging interest in berries for bone health. RECENT FINDINGS: Recent studies indicate that berry intakes are relevant to prevent osteopenia in humans. Their bone-sparing effects can be partly explained by their content in phytochemicals and vitamins. Beyond their antioxidant or anti-inflammatory functions, those micronutrients have been shown to modulate enzyme activities, cellular signaling pathways, and gene expression. SUMMARY: Berry-enriched foods represent a relevant opportunity in the design of nutritional strategies targeting bone alteration.

Pinoresinol of olive oil decreases vitamin D intestinal absorption.

Enriching oils, such as olive oil, could be one solution to tackle the worldwide epidemic of vitamin D deficiency and to better fit with omega 3 (DHA) recommendations. However, data regarding the interactions occurring at the intestinal level between vitamin D and phenols from olive oil are scarce. We first determined the effect of polyphenols from a virgin olive oil, and a virgin olive oil enriched with DHA, on vitamin D absorption in rats. We then investigated the effects of 3 main olive oil phenols (oleuropein, hydroxytyrosol and pinoresinol) on vitamin D uptake by Caco-2 cells. The presence of polyphenols in the olive oil supplemented with DHA inhibited vitamin D postprandial response in rats (-25%, p<0.05). Similar results were obtained with a mix of the 3 polyphenols delivered to Caco-2 cells. However, this inhibitory effect was due to the presence of pinoresinol only. As the pinoresinol content can highly vary between olive oils, the present results should be taken into account to formulate an appropriate oil product enriched in vitamin D.

The phenolic acids of Agen prunes (dried plums) or Agen prune juice concentrates do not account for the protective action on bone in a rat model of postmenopausal osteoporosis.

Dietary supplementation with dried plum (DP) has been shown to protect against and reverse established osteopenia in ovariectomized rodents. Based on in vitro studies, we hypothesized that DP polyphenols may be responsible for that bone-sparing effect. This study was designed to (1) analyze whether the main phenolic acids of DP control preosteoblast proliferation and activity in vitro; (2) determine if the polyphenolic content of DP or DP juice concentrate is the main component improving bone health in vivo; and (3) analyze whether DP metabolites directly modulate preosteoblast physiology ex vivo. In vitro, we found that neochlorogenic, chlorogenic, and caffeic acids induce the proliferation and repress the alkaline phosphatase activity of primary preosteoblasts in a dose-dependent manner. In vivo, low-chlorogenic acid Agen prunes (AP) enriched with a high-fiber diet and low-chlorogenic acid AP juice concentrate prevented the decrease of total femoral bone mineral density induced by estrogen deficiency in 5-month-old female rats and positively restored the variations of the bone markers osteocalcin and deoxypyridinoline. Ex vivo, we demonstrated that serum from rats fed with low-chlorogenic acid AP enriched with a high-fiber diet showed repressed proliferation and stimulated alkaline phosphatase activity of primary preosteoblasts. Overall, the beneficial action of AP on bone health was not dependent on its polyphenolic content.

GPR40, a free fatty acid receptor, differentially impacts osteoblast behavior depending on differentiation stage and environment.

GPR40 is a free fatty acid receptor that has been recently shown to impact bone remodeling. This receptor protects skeleton by inhibiting bone resorbing osteoclast differentiation. Consistent with GPR40 expression on bone forming cells, we assumed that this receptor may also influence osteoblast activity. To further investigate this hypothesis, biological effects of GW9508, a synthetic agonist for GPR40, was first tested on osteoblast differentiation parameters. Assays were performed in two different cell models: the MC3T3-E1 osteoblastic cell line and primary bone marrow cultures extracted from wild-type and GPR40 knock-out mice. Both models showed a dual role of GPR40 on osteoblasts. Although receptor stimulation induced early stimulation of differentiation marker expression, it finally led to inhibition of mineralization process during late differentiation stages. To further elucidate this discrepancy, mice were ovariectomized to induce bone loss and received GPR40 agonist by gavage. Data revealed a weak influence of GPR40 agonist on osteoblast markers expression. Nevertheless, a significant increase in OPG expression was observed upon GW9508 treatment that contribute to explain the GPR40-related osteoporosis prevention. To conclude, our results confirm the relevance of this new opportunity in the management of bone loss.

Towards human exploration of space: The THESEUS review series on nutrition and metabolism research priorities.

Nutrition has multiple roles during space flight from providing sufficient nutrients to meet the metabolic needs of the body and to maintain good health, to the beneficial psychosocial aspects related to the meals. Nutrition is central to the functioning of the body; poor nutrition compromises all the physiological systems. Nutrition is therefore likely to have a key role in counteracting the negative effects of space flight (e.g., radiation, immune deficits, oxidative stress, and bone and muscle loss). As missions increase in duration, any dietary/nutritional deficiencies will become progressively more detrimental. Moreover, it has been recognized that the human diet contains, in addition to essential macronutrients, a complex array of naturally occurring bioactive micronutrients that may confer significant long-term health benefits. It is therefore critical that astronauts be adequately nourished during missions. Problems of nutritional origin are often treatable by simply providing the appropriate nutrients and adequate recommendations. This review highlights six key issues that have been identified as space research priorities in nutrition field: in-flight energy balance; altered feeding behavior; development of metabolic stress; micronutrient deficiency; alteration of gut microflora; and altered fluid and electrolytes balance. For each of these topics, relevance for space exploration, knowledge gaps and proposed investigations are described. Finally, the nutritional questions related to bioastronautics research are very relevant to multiple ground-based-related health issues. The potential spin-offs are both interesting scientifically and potentially of great clinical importance.

Pomegranate Peel Extract Prevents Bone Loss in a Preclinical Model of Osteoporosis and Stimulates Osteoblastic Differentiation in Vitro.

The nutritional benefits of pomegranate have attracted great scientific interest. The pomegranate, including the pomegranate peel, has been used worldwide for many years as a fruit with medicinal activity, mostly antioxidant properties. Among chronic diseases, osteoporosis, which is associated with bone remodelling impairment leading to progressive bone loss, could eventually benefit from antioxidant compounds because of the involvement of oxidative stress in the pathogenesis of osteopenia. In this study, with in vivo and ex vivo experiments, we investigated whether the consumption of pomegranate peel extract (PGPE) could limit the process of osteopenia. We demonstrated that in ovariectomized (OVX) C57BL/6J mice, PGPE consumption was able to significantly prevent the decrease in bone mineral density (-31.9%; p < 0.001 vs. OVX mice) and bone microarchitecture impairment. Moreover, the exposure of RAW264.7 cells to serum harvested from mice that had been given a PGPE-enriched diet elicited reduced osteoclast differentiation and bone resorption, as shown by the inhibition of the major osteoclast markers. In addition, PGPE appeared to substantially stimulate osteoblastic MC3T3-E1 alkaline phosphatase (ALP) activity at day 7, mineralization at day 21 and the transcription level of osteogenic markers. PGPE may be effective in preventing the bone loss associated with ovariectomy in mice, and offers a promising alternative for the nutritional management of this disease.

Pros and cons of fatty acids in bone biology.

Despite the growing interest in deciphering the causes and consequences of obesity-related disorders, the mechanisms linking fat intake to bone behaviour remain unclear. Since bone fractures are widely associated with increased morbidity and mortality, most notably in elderly and obese people, bone health has become a major social and economic issue. Consistently, public health system guidelines have encouraged low-fat diets in order to reduce associated complications. However, from a bone point of view, mechanisms linking fat intake to bone alteration remain quite controversial. Thus, after more than a decade of dedicated studies, this timely review offers a comprehensive overview of the relationships between bone and fatty acids. Using clinical evidences as a starting-point to more complex molecular elucidation, this work highlights the complexity of the system and reveals that bone alteration that cannot be solved simply by taking ω-3 pills. Fatty acid effects on bone metabolism can be both direct and indirect and require integrated investigations. Furthermore, even at the level of a single cell, one fatty acid is able to trigger several different independent pathways (receptors, metabolites…) which may all have a say in the final cellular metabolic response.

Muscle and bone, two interconnected tissues.

As bones are levers for skeletal muscle to exert forces, both are complementary and essential for locomotion and individual autonomy. In the past decades, the idea of a bone-muscle unit has emerged. Numerous studies have confirmed this hypothesis from in utero to aging works. Space flight, bed rest as well as osteoporosis and sarcopenia experimentations have allowed to accumulate considerable evidence. Mechanical loading is a key mechanism linking both tissues with a central promoting role of physical activity. Moreover, the skeletal muscle secretome accounts various molecules that affect bone including insulin-like growth factor-1 (IGF-1), basic fibroblast growth factor (FGF-2), interleukin-6 (IL-6), IL-15, myostatin, osteoglycin (OGN), FAM5C, Tmem119 and osteoactivin. Even though studies on the potential effects of bone on muscle metabolism are sparse, few osteokines have been identified. Prostaglandin E2 (PGE2) and Wnt3a, which are secreted by osteocytes, osteocalcin (OCN) and IGF-1, which are produced by osteoblasts and sclerostin which is secreted by both cell types, might impact skeletal muscle cells. Cartilage and adipose tissue are also likely to participate to this control loop and should not be set aside. Indeed, chondrocytes are known to secrete Dickkopf-1 (DKK-1) and Indian hedgehog (Ihh) and adipocytes produce leptin, adiponectin and IL-6, which potentially modulate bone and muscle metabolisms. The understanding of this system will enable to define new levers to prevent/treat sarcopenia and osteoporosis at the same time. These strategies might include nutritional interventions and physical exercise.

Deficiency of G-protein coupled receptor 40, a lipid-activated receptor, heightens in vitro- and in vivo-induced murine osteoarthritis.

Osteoarthritis (OA) is an age-related degenerative joint disease. To date, its management is focused on symptoms (pain and inflammation). Studies suggest that fatty acids can reduce the expression of inflammatory and catalytic mediators, and improve in vivo joint function. Free fatty acid receptors (FFARs) such as G-protein coupled receptor 40 (GPR40) are proposed as attractive therapeutic targets to counteract inflammation and cartilage degradation observed in OA. This study aims to elucidate the involvement of GPR40 in OA. In this study, we used an in vitro model of OA, and surgically induced OA by ligament transection and partial meniscectomy in wild-type and GPR40 deficient mice. OA phenotype was investigated in vivo by histology and genes expression. We demonstrate that IL-1ß-treated GPR40(-/-) chondrocytes secret more inflammatory mediators (nitric oxide, interleukin-6, prostaglandin E2) and active catabolic enzymes (metalloproteinase-2, -9 [MMP-2, MMP-9]), and show decreased anabolism (glycoaminoglycan) compared to GPR40(+/+) cells. In accordance with these results, we show that GPR40(-/-) mice exhibit an aggravated OA-induced phenotype characterized by higher tidemark exposure, frequency of osteophyte formation and subchondral bone sclerosis. Altogether our results demonstrate that GPR40 deficiency leads to an extended OA phenotype, providing evidence that increasing GPR40 activity, by natural or synthetic ligands, could be a new strategy in the management of OA.

Increased body fat mass and tissue lipotoxicity associated with ovariectomy or high-fat diet differentially affects bone and skeletal muscle metabolism in rats.

PURPOSE: The aim of this study was to evaluate and compare the musculoskeletal effects induced by ovariectomy-related fat mass deposition against the musculoskeletal effects caused by a high-fat diet. METHODS: A group of adult female rats was ovariectomized and fed a control diet. Two additional groups were sham-operated and fed a control or a high-fat diet for 19 weeks. Distal femur and serum bone parameters were measured to assess bone metabolism. Muscle protein metabolism, mitochondrial markers and triglyceride content were evaluated in tibialis anterior. Triglyceride content was evaluated in liver. Circulating inflammatory and metabolic markers were determined. RESULTS: The high-fat diet and ovariectomy led to similar increases in fat mass (+36.6-56.7%; p < 0.05) but had different impacts on bone and muscle tissues and inflammatory markers. Consumption of the high-fat diet led to decreased bone formation (-38.4%; p < 0.05), impaired muscle mitochondrial metabolism, muscle lipotoxicity and a 20.9% increase in tibialis anterior protein synthesis rate (p < 0.05). Ovariectomy was associated with higher bone turnover as bone formation increased +72.7% (p < 0.05) and bone resorption increased +76.4% (p < 0.05), leading to bone loss, a 17.9% decrease in muscle protein synthesis rate (p < 0.05) and liver lipotoxicity. CONCLUSIONS: In female rats, high-fat diet and ovariectomy triggered similar gains in fat mass but had different impacts on bone and muscle metabolism. The ovariectomy-induced mechanisms affecting the musculoskeletal system are mainly caused by estrogen depletion, which surpasses the potential-independent effect of adiposity.

Nutraceuticals in joint health: animal models as instrumental tools.

Osteoarthritis (OA) is a degenerative joint disease with no curative treatments. Many studies have begun to demonstrate the efficacy of nutraceuticals for slowing down OA. Animal models are utilized as a compulsory step in demonstrating the protective potential of these compounds on joint health. Nevertheless, there exist a wide variety of available OA models and selecting a suitable system for evaluating the effects of a specific compound remains difficult. Here, we discuss animal studies that have investigated nutraceutical effects on OA. In particular, we highlight the large spectrum of animal models that are currently accepted for examining the OA-related effects of nutraceuticals, giving recommendations for their use.

The flavonoid fisetin promotes osteoblasts differentiation through Runx2 transcriptional activity.

SCOPE: Flavonoids represent a group of polyphenolic compounds commonly found in daily nutrition with proven health benefits. Among this group, the flavonol fisetin has been previously shown to protect bone by repressing osteoclast differentiation. In the present study, we investigated the role of fisetin in regulating osteoblasts physiology. METHODS AND RESULTS: In vivo mice treated with LPSs exhibited osteoporosis features associated with a dramatic repression of osteoblast marker expression. In this model, inhibition of osteocalcin and type I collagen alpha 1 transcription was partially countered by a daily consumption of fisetin. Interestingly, in vitro, fisetin promoted both osteoblast alkaline phosphatase activity and mineralization process. To decipher how fisetin may exert its positive effect on osteoblastogenesis, we analyzed its ability to control the runt-related transcription factor 2 (Runx2), a key organizer in developing and maturing osteoblasts. While fisetin did not impact Runx2 mRNA and protein levels, it upregulated its transcriptional activity. Actually, fisetin stimulated the luciferase activity of a reporter plasmid driven by the osteocalcin gene promoter that contains Runx2 binding sites and promoted the mRNA expression of osteocalcin and type I collagen alpha 1 targets. CONCLUSION: Bone sparing properties of fisetin also rely on its positive influence on osteoblast differentiation and activity.

Pomegranate and its derivatives can improve bone health through decreased inflammation and oxidative stress in an animal model of postmenopausal osteoporosis.

PURPOSE: Recently, nutritional and pharmaceutical benefits of pomegranate (PG) have raised a growing scientific interest. Since PG is endowed with anti-inflammatory and antioxidant activities, we hypothesized that it may have beneficial effects on osteoporosis. METHODS: We used ovariectomized (OVX) mice as a well-described model of postmenopausal osteoporosis to study the influence of PG consumption on bone health. Mice were divided into five groups as following: two control groups sham-operated and ovariectomized (OVX CT) mice fed a standard diet, versus three treated groups OVX mice given a modified diet from the AIN-93G diet, containing 5.7% of PG lyophilized mashed totum (OVX PGt), or 9.6% of PG fresh juice (OVX PGj) or 2.9% of PG lyophilized mashed peel (OVX PGp). RESULTS: As expected, ovariectomy was associated with a decreased femoral bone mineral density (BMD) and impaired bone micro-architecture parameters. Consumption of PGj, PGp, or PGt induced bone-sparing effects in those OVX mice, both on femoral BMD and bone micro-architecture parameters. In addition, PG (whatever the part) up-regulated osteoblast activity and decreased the expression of osteoclast markers, when compared to what was observed in OVX CT animals. Consistent with the data related to bone parameters, PG consumption elicited a lower expression of pro-inflammatory makers and of enzymes involved in ROS generation, whereas the expression of anti-inflammatory markers and anti-oxidant actors was enhanced. CONCLUSION: These results indicate that all PG parts are effective in preventing the development of bone loss induced by ovariectomy in mice. Such an effect could be partially explained by an improved inflammatory and oxidative status.