The main aim of this study was to investigate the bone-sparing effect of hesperidin, one of the main flavonoid present in oranges, in two age groups of ovariectomized female rats, compared with their intact controls. Young (3 mo) and adult (6 mo) female Wistar rats were sham operated (SH) or ovariectomized (OVX) and then pair-fed for 90 days a casein-based diet supplemented or not with 0.5% hesperidin (Hp; n = 10/group). In older rats, Hp intake led to a partial inhibition of OVX-induced bone loss, whereas a complete inhibition was obtained in younger animals. At both ages, while plasma osteocalcin concentrations were unchanged, urinary excretion of deoxypyridinoline was reduced by Hp intake, suggesting that Hp was able to slow down bone resorption. Unexpectedly, in intact young rats, Hp consumption resulted in a significant increase in bone mineral density (BMD). Indeed, 6-mo-old HpSH rats had a similar BMD to 9-mo-old nontreated SH adult rats, suggesting an accelerated bone mass gain in the young rats. In contrast, in intact adult rats, Hp did not further increase BMD but did improve their bone strength. The results of this study show a protective effect of Hp on bone loss in OVX rats of both ages without uterine stimulation and accompanied by a lipid-lowering effect. The unexpected and intriguing findings obtained in intact rats showing improved BMD in young rats and improved femoral load in adult rats merit further investigation. The bone and lipid benefits of hesperidin make it an attractive dietary agent for the management of the health of postmenopausal women.

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Recent research has provided insights into dietary components that may optimise bone health and stimulate bone formation. Fruit and vegetable intake, as well as grains and other plant-derived food, have been linked to decreased risk of major chronic diseases including osteoporosis. This effect has been partially attributed to the polyphenols found in these foods. Thus, it has been suggested that these compounds may provide desirable bone health benefits through an action on bone cell metabolism. The present review will focus on how some polyphenols can modulate osteoblast function and reports which cellular signalling pathways are potentially implicated. However, to date, despite numerous investigations, few studies have provided clear evidence that phenolic compounds can act on osteoblasts. Polyphenols cited in the present review seem to be able to modulate the expression of transcription factors such as runt-related transcription factor-2 (Runx2) and Osterix, NF-κB and activator protein-1 (AP-1). It appears that polyphenols may act on cellular signalling such as mitogen-activated protein kinase (MAPK), bone morphogenetic protein (BMP), oestrogen receptor and osteoprotegerin/receptor activator of NF-κB ligand (OPG/RANKL) and thus may affect osteoblast functions. However, it is also important to take in account the possible interaction of these compounds on osteoclast metabolism to better understand the positive correlation reported between the consumption of fruit and vegetables and bone mass.

Hesperidin (Hp), a citrus flavonoid predominantly found in oranges, shows bone-sparing effects in ovariectomised (OVX) animals. In human subjects, the bioavailability of Hp can be improved by the removal of the rhamnose group to yield hesperetin-7-glucoside (H-7-glc). The aim of the present work was to test whether H-7-glc was more bioavailable and therefore more effective than Hp in the prevention of bone loss in the OVX rat. Adult 6-month-old female Wistar rats were sham operated or OVX, then pair fed for 90 d a casein-based diet supplemented or not with freeze-dried orange juice enriched with Hp or H-7-glc at two dose equivalents of the hesperetin aglycone (0·25 and 0·5 %). In the rats fed 0·5 %, a reduction in OVX-induced bone loss was observed regarding total bone mineral density (BMD): þ 7·0 % in OVX rats treated with Hp (HpOVX) and þ 6·6 % in OVX rats treated with H-7-glc (H-7-glcOVX) v. OVX controls (P,0·05). In the rats fed 0·25 % hesperetin equivalents, the H-7-glcOVX group showed a 6·6 % improvement in total femoral BMD v. the OVX controls (P,0·05), whereas the Hp diet had no effect at this dose. The BMD of rats fed 0·25 % H-7-glc was equal to that of those given 0·5 % Hp, but was not further increased at 0·5 % H-7-glc. Plasma hesperetin levels and relative urinary excretion were significantly enhanced in the H-7-glc v. Hp groups, and the metabolite profile showed the absence of eriodictyol metabolites and increased levels of hesperetin sulphates. Taken together, improved bioavailability of H-7-glc may explain the more efficient bone protection of this compound.Bioavailability: Bone mineral density: Hesperidin: Flavanones: Rats Nutrition plays an important role in the dietary management and prevention of osteoporosis, a major public health problem. While it is established that Ca, vitamin D and micronutrients are essential for bone health, other compounds such as polyphenols, found abundantly in fruit and vegetables, show potential for bone-protective effects. For example, rodent studies have shown that quercetin and quercetin-3-rhamnoglucoside (rutin) from onions (1,2) , resveratrol from red wine (3) and isoflavones from soya (4) inhibit ovariectomised (OVX)-induced bone loss. Until now, most of the human intervention studies have been carried out with high levels of soya isoflavones (80-90 mg), some studies showing prevention of bone loss in postmenopausal women (5,6) , while others not (7,8) . The level of consumption of soya products is rather low in Western countries compared with Asian ones, whose daily intakes average 20 -40 mg (9) . Therefore, it would be of interest to identify commonly consumed polyphenols with bone-protective effects, as soya is not used as a staple in the Western diet.Hesperidin (Hp), a monomethoxylated flavanone found abundantly in citrus fruits such as oranges (10) , is highly consumed in Western countries. Indeed, in Finland, Hp consumption was estimated to be 28 mg/d, contributing to 50 % of total flavonoid intake (11) . Hp and metabolites show promising health benefit...