Glucocorticoid-induced osteoporosis: pathogenesis,diagnosis, and management

Glucocorticoid-induced bone loss is dose- and duration-related, develops rapidly (within months of therapy), and leads to an increased risk of fractures. Moreover, less than one in four patients prescribed oral glucocorticoids receive any treatment to prevent or treat osteoporosis. The American College of Rheumatology recommends bisphosphonate therapy to prevent bone loss in most patients beginning long-term glucocorticoid therapy (prednisone equivalent of > or =5 mg/day for at least 3 months), and in men and postmenopausal women receiving long-term glucocorticoids who have an abnormal bone mineral density (T score below -1). Patients with glucocorticoid-induced osteoporosis are at particularly high risk for fractures, and should be treated aggressively to reduce fracture risk. Risedronate is approved in the United States for both prevention and treatment of glucocorticoid-induced osteoporosis and alendronate is approved for treatment. Both drugs increase bone mass in patients with established glucocorticoid-induced osteoporosis. Risedronate has been shown to significantly reduce the incidence of fractures after 1 year of treatment. Prevention or treatment of glucocorticoid-induced bone loss is recommended for patients at risk.     

An Evaluation of Managing and Educating Patients on the Risk of Glucocorticoid-Induced Osteoporosis

OBJECTIVE: To assess the impact of risk management activities on patient risk of glucocorticoid-induced osteoporosis. METHODS: Ninety-six adult patients taking chronic glucocorticoid therapy in 15 community pharmacies. Patients in the control group received usual and customary care. Patients in the treatment pharmacies received education and an educational pamphlet about the risks of glucocorticoid-induced osteoporosis. In addition, the treatment group pharmacists monitored the patients' drug therapy, to identify and address drug-related problems. Data including the glucocorticoid taken by the patient, medications, and osteoporosis risk factors were collected at baseline and after 9 months of monitoring, via Web-based survey completed in the pharmacy. Using an intent to treat approach, the pre-post frequency changes were compared with contrasts for presence of bisphosphonate therapy, presence of estrogen therapy, presence of calcium supplement, discussion of glucocorticoid-induced osteoporosis risk, discussion of bone density test, presence of bone mineral density test, reported inactivity, and reported low calcium diet. RESULTS: The contrast was significant in favor of the treatment pharmacies for the frequency of patients taking a calcium supplement (Control [-6.9%] vs. Treatment [17.1%], P < 0.05). No other contrast was significant. CONCLUSIONS: Community pharmacists are capable of increasing calcium supplementation among patients at risk for glucocorticoid-induced osteoporosis. Pharmacists who educate at-risk patients can impact the self-care of these patients.     

Glucocorticoid-induced osteoporosis

Glucocorticoids are the most common cause of drug-induced osteoporosis. Given the widespread use of oral glucocorticoids in the treatment of autoimmune, pulmonary, gastrointestinal disorders and organ transplantation, attention to glucocorticoid-induced osteoporosis has substantially increased. Bone loss occurs rapidly in the first few months of glucocorticoid therapy. Trabecular bone is affected more than cortical bone. Glucocorticoid treatment is associated with a substantially increased risk of fractures, particularly hip and vertebral fractures. The skeletal effects of glucocorticoids are both dose- and duration-dependent. The patophysiology of glucocorticoid-induced osteoporosis is a complex process, several mechanisms are proposed but not yet fully highlighted. Despite several evidence-based guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis and the availability of effective therapeutic options, the proportion of individuals with appropriate evaluation and treatment remains relatively low.     

Glucocorticoid-induced osteoporosis

Chronic glucocorticoid treatment is the most frequent cause of secondary osteoporosis. The direct inhibitory effect of glucocorticoids on osteoblasts results in decreased bone formation. Increased osteoclastic bone resorption due to low concentrations of gonadal steroid hormones and glucocorticoid-induced direct suppression of intestinal calcium absorption also contribute to the decrease of bone mass in these patients. Bone loss is rapid, particularly in the first months of glucocorticoid therapy. Bone mineral density of the lumbar spine and proximal femur should be measured in patients who are starting chronic therapy with glucocorticoids. Although glucocorticoid-induced osteoporosis is a severe and nowadays partially preventable disorder, osteoporosis prophylaxis is only rarely prescribed to these patients. Recent randomized, controlled trials proved the therapeutic effects of hormone replacement therapy, as well as of bisphosphonates and active vitamin D analogs in primary and secondary prevention of glucocorticoid-induced osteoporosis.     

儿童糖皮质激素性骨质疏松的防治

糖皮质激素在儿科疾病中应用广泛,长期应用糖皮质激素可导致骨密度减低及骨折等。在成人,存在管理糖皮质激素性骨质疏松症的循证指南,儿童糖皮质激素性骨质疏松症也越来越受到儿科医师的重视,但有关儿童的信息还是非常少,本文主要对儿童糖皮质激素性骨质疏松的预防和治疗进行综述。     

The Nutraceutical Genistein-Lycopene Combination Improves Bone Damage Induced by Glucocorticoids by Stimulating the Osteoblast Formation Process

Chronic glucocorticoid (GC) therapy is the most common cause of iatrogenic osteoporosis and represents an important risk factor for osteoporosis and bone fractures. New therapeutic approaches are required in order to treat osteoporosis and reduce the side effects related to the use of anti-osteoporotic drugs. In this context, previous studies reported the efficacy of some isoflavones and carotenoids, such as lycopene and genistein, on the reduction of the risk of fracture related to osteoporosis. The aim of this study was to investigate the effects of a combined oral treatment, consisting of genistein and lycopene, in an experimental model of glucocorticoid-induced osteoporosis (GIO). GIO was induced by subcutaneous injection of methylprednisolone (MP, 30 mg/kg) for 60 days, whereas the control group (Sham) received saline solution only. Following induction, MP animals randomly were assigned to receive alendronate, genistein, lycopene, or the association of genistein and lycopene or saline solution for additional 60 days together with MP. Femurs obtained from the Sham group were used for osteoblasts extraction; they were then incubated with dexamethasone (DEX) for 24 h to be then treated with lycopene or genistein or the association of lycopene and genistein for an additional 24 h. Treatments with lycopene and genistein restored the impaired mineralization of cells observed following DEX treatment and stimulated osteoblast differentiation by increasing the depressed expression of bALP and RUNX2 (p < 0.0001). Wnt5a, β-catenin, and Nrf-2 expression were significantly increased following genistein and lycopene treatment (p < 0.0001), thus confirming their antioxidant activity as well as their ability in stimulating osteoblast function, mostly when genistein and lycopene were used in association. The combined treatment of genistein and lycopene improved the bone damage induced by glucocorticoids and significantly restored the normal architecture of bones as well as adequate interconnectivity of bone trabeculae, thus increasing bone mineral density parameters. The obtained data demonstrated that genistein and lycopene but in particular their association might prevent GC’s adverse effects, thus stimulating bone formation and reducing bone resorption, improving bone structure and microarchitecture, through different molecular pathways, such as the Wnt/β-catenin and the Nrf-2 signaling.     

Genetic background of osteoporosis

Osteoporosis is characterized by a decrease in bone mass as well as a deterioration of the bone architecture resulting in an increased risk of fracture. The disease is multifactorial, and it depends on environmental and genetic factors. Twin studies have shown that genetic factors account for 60-80% of the variance in bone mineral density, the best predictor of the risk of osteoporosis. There are different approaches to identify these genetic factors. Linkage studies in human and experimental animals have defined multiple loci that regulate bone mass but most of the genes responsible for this effect remain to be defined. The 11q12-13 locus was the first that was linked to bone mineral density of the young female and special bone diseases like high bone mass syndrome and osteoporosis-pseudoglioma syndrome. Both diseases appear to be in association with LDL receptor-related protein 5 gene mutation. The effect of LDL receptor-related protein 5 on bone metabolism had not been known only genetic methods suggested it. The effect of LRP5 in osteoporosis pathogenesis requires more investigation. Association and linkage studies have been performed in order to identify candidate genes in the pathogenesis of osteoporosis. Vitamin D receptor gene was the first candidate, however its effect is controversial. Other candidates, such as insulin like growth factor, interleukin-6, estrogen receptor alpha, transforming growth factor beta show no or small effect on bone mineral density or fracture frequency. To date only Sp1 polymorphism of collagen gene seems to have a consistent effect on bone fragility. The improved understanding of osteoporosis genetics should lead to better diagnosis of this disease and new treatment and prevention strategies.     

Management of Postmenopausal Osteoporosis

Postmenopausal osteoporosis is a very common disease, and approximately half of all women aged >50 years will experience an osteoporotic fracture during the remainder of their lifetime. The predominant cause of postmenopausal osteoporosis is the decline in estrogen levels, which causes an increase in bone turnover, and results in a loss of bone mass throughout the entire skeleton. Fragility fractures, either vertebral or nonvertebral, have a considerable adverse effect on quality of life in women with osteoporosis and place a significant burden on society in terms of healthcare costs.Management of postmenopausal osteoporosis includes alteration of modifiable risk factors (e.g. lifestyle and propensity to fall), ensuring adequate calcium and vitamin D intake, and pharmacological treatment to decrease fracture risk by slowing or preventing bone loss and preserving bone strength. Raloxifene (Evista®), a selective estrogen receptor modulator that partially mimics the effects of estrogen on bone and lipid metabolism and acts as an antiestrogen in the breast and endometrium, is indicated for the prevention and treatment of postmenopausal osteoporosis. Raloxifene increases bone mineral density at vertebral and nonvertebral sites, and decreases the risk of vertebral fracture to a similar extent to the bisphosphonates alendronate and risedronate. However, effects on nonvertebral fracture risk, including the risk of hip fracture, have not been observed.Raloxifene appears to reduce breast cancer risk (in women at average risk) and cardiovascular risk (in women at increased risk) without stimulating the endometrium, and does not cause vaginal bleeding or breast pain. However, the drug causes hot flashes in some women, and increases the risk of venous thromboembolic events by about the same amount as hormone replacement therapy (HRT).In economic models, raloxifene is cost effective compared with no treatment, HRT, calcitonin, or alendronate for the prevention or treatment of postmenopausal osteoporosis.In conclusion, raloxifene is a valuable and cost-effective therapy for preventing the progression of osteoporosis and for reducing vertebral fracture risk in osteoporotic postmenopausal women. The tendency for raloxifene to cause hot flashes, and its apparent lack of effect on hip fracture risk, may preclude its use in women with vasomotor symptoms and in patients at high risk for hip fracture. Results from large ongoing trials are needed to confirm the effects of raloxifene on breast cancer and cardiovascular disease. However, the effects of raloxifene on breast cancer and cardiovascular risk without stimulating the endometrium make the drug an attractive therapy for the prevention and treatment of postmenopausal osteoporosis.     

Recent progress in understanding the genetic susceptibility to osteoporosis

Family and twin studies have established a genetic contribution to the etiology of osteoporosis. The genes and allelic variants conferring osteoporotic risk are largely undefined, but the number of candidates has increased steadily in recent years (Table I). Osteoporosis is a complex disease, and allelic variation in many other candidate-genes including those that encode growth factors, cytokines, calciotropic hormones, and bone matrix proteins are likely to also play a role and warrant systematic investigation. Most family and association studies to date have focused on the genetic contributions to bone density, a major determinant of bone strength and fracture risk. Bone density is not the only determinant of skeletal fragility, however, and genetic influences on fracture risk are independent of bone density [Cummings et al., 1995]. The microarchitectural properties and overall size and geometry of bone also influence skeletal strength [Bouxsein et al., 1996], and the genetic influences on these phenotypes should be investigated more rigorously. Even fewer studies have assessed the association between candidate-gene variation and the risk of fracture, the most important clinical outcome of osteoporosis. Large-scale molecular epidemiologic studies will be increasingly necessary in the future to quantify the relative, absolute and attributable risks of fracture associated with specific genetic variants. Osteoporosis is a complex, multifactorial disease, and most candidate-gene association studies have had limited statistical power to assess gene-gene and gene-environment interaction. Although gender plays an important role in the development of osteoporosis, genetic studies have almost exclusively focused on women, and have not tested whether gender modifies the association between genetic variation and osteoporotic risk. Therefore, future genetic studies will need to recruit larger samples of individuals including men. Rapid additional progress in our understanding of the molecular basis of osteoporosis can be expected in the near future as ongoing genome-wide linkage [Spotila et al., 1996] and candidate-gene association analyses are completed. Linkage analyses in families at high-risk for rare metabolic bone diseases should also yield important clues to the pathogenesis of osteoporosis. Recent examples are the mapping of loci for both high [Johnson et al., 1997] and low [Gong et al., 1996] bone mass to chromosome 11q and osteopetrosis to chromosome 1p [Van Hul et al., 1997]. Similar ongoing studies in baboons [Rogers and Hixson, 1997] and mice [Beamer et al., 1997] may reveal additional loci whose human homologs contribute to osteoporotic risk. The improved understanding of osteoporosis that will emerge from these genetic studies should lead to better diagnosis of this disease and new treatment and prevention strategies.     

Genetics of osteoporosis

Osteoporosis is a common disease with a strong genetic component characterised by reduced bone mass and an increased risk of fragility fractures. Twin and family studies have shown that genetic factors contribute to osteoporosis by influencing bone mineral density (BMD), and other phenotypes that are associated with fracture risk, although the heritability of fracture itself is modest. Linkage studies have identified several quantitative trait loci that regulate BMD but most causal genes remain to be identified. In contrast, linkage studies in monogenic bone diseases have been successful in gene identification, and polymorphisms in many of these genes have been found to contribute to the regulation of bone mass in the normal population. Population-based studies have identified polymorphisms in several candidate genes that have been associated with bone mass or osteoporotic fracture, although individually these polymorphisms only account for a small amount of the genetic contribution to BMD regulation. Environmental factors such as diet and physical activity are also important determinants of BMD, and in some cases specific nutrients have been found to interact with genetic polymorphisms to regulate BMD. From a clinical standpoint, advances in knowledge about the genetic basis of osteoporosis are likely to be important in increasing the understanding of the pathophysiology of the disease; providing new genetic markers with which to assess fracture risk and in identifying genes and pathways that form molecular targets for the design of the next generation of drug treatments.     

Alternative therapies for the prevention and treatment of osteoporosis

Osteoporosis is a medical condition that affects millions of men and women. People with this condition have low bone mass, which places them at increased risk for bone fracture after minor trauma. The surgeries and treatments required to repair and heal bone fractures involve long recovery periods and can be expensive. Because osteoporosis occurs frequently in the elderly, the financial burden it places on society is likely to be large. In the United States, the Food and Drug Administration has approved several drugs for use in the prevention and treatment of osteoporosis. However, all of the currently available agents have severe side effects that limit their efficacy and underscore the urgent need for new treatment options. One promising approach is the development of alternative (nonpharmaceutical) strategies for bone maintenance, as well as for the prevention and treatment of osteoporosis. This review examines the currently available nonpharmaceutical alternatives that have been evaluated in in vitro and in vivo studies. Certain plants from the following families have shown the greatest benefits on bone: Alliceae, Asteraceae, Thecaceae, Fabaceae, Oleaceae, Rosaceae, Ranunculaceae, Vitaceae, Zingiberaceae. The present review discusses the most promising findings from studies of these plant families.     

Impact and risk factors of post-stroke bone fracture

Bone fracture occurs in stroke patients at different times during the recovery phase, prolonging recovery time and increasing medical costs. In this review, we discuss the potential risk factors for post-stroke bone fracture and preventive methods. Most post-stroke bone fractures occur in the lower extremities, indicating fragile bones are a risk factor. Motor changes, including posture, mobility, and balance post-stroke contribute to bone loss and thus increase risk of bone fracture. Bone mineral density is a useful indicator for bone resorption, useful to identify patients at risk of post-stroke bone fracture. Calcium supplementation was previously regarded as a useful treatment during physical rehabilitation. However, recent data suggests calcium supplementation has a negative impact on atherosclerotic conditions. Vitamin D intake may prevent osteoporosis and fractures in patients with stroke. Although drugs such as teriparatide show some benefits in preventing osteoporosis, additional clinical trials are needed to determine the most effective conditions for post-stroke applications.     

Use of bone turnover markers in clinical osteoporosis assessment in women: current issues and future options

Monitoring bone turnover of the adult and aging skeleton is essential for optimal treatment of bone metabolic diseases, such as postmenopausal osteoporosis. Diagnosis of osteoporosis is based solely on dual-emission x-ray absorptiometry-based measurements of bone mineral density. However, within the last 20 years, biochemical markers of bone turnover have been implemented to a larger degree, and especially within the field of drug development. Numerous clinical studies have underscored that the markers have promise in terms of predicting patients at high risk of losing bone, future fracture events and importantly also the fracture efficacy of drugs in development. Furthermore, while classical methods often require years to monitor the changes, the bone turnover markers do so within a shorter time span. The aims of this article are to provide an update on the different biochemical markers of bone turnover, and to give an overview of their applications in epidemiological and clinical research especially in women. The main emphasis will be on their utility in clinical trials testing the efficacy of drugs for the treatment of osteoporosis, and their ability to supplement bone mass measurements. Finally, recent evidence suggests that biochemical markers may provide information on bone age that may indirectly relate to bone quality, and this is discussed together with future possibilities for measuring bone quality using bone turnover markers. In summary, a more targeted use of biomarkers could assist in the identification of high-risk patients, the process of drug discovery and monitoring of the efficacy of osteoporosis treatment in clinical settings.     

Effectiveness of screening for osteoporosis by bone density measurement for the prevention of fractures: a review of the evidence

To review evidence on the benefits of screening women and men for osteoporosis, a Pub Med search was performed in English papers published between 1990 and 2002. We used data from a cohort study to estimate risk of fracture from bone mineral density. Bone mineral density measured by dual X-ray absorptiometry (DXA) can predict bone fracture among elderly women, peri- and early post-menopausal women, and elderly men. It is recommended that all white women older than 65 years be screened routinely for osteoporosis. We suggest that Japanese elderly women should receive BMD measurements as a screening, but we have still issues to be solved including age from when the screening should be started, methods, and how to treat the women found to have osteoporosis at the screening. For peri- and postmenopausal women and elderly men, it might be beneficial to measure BMD as a screening and start treatment for those patients found to have osteoporosis. However, incidence of fractures for these people is lower than that for elderly women. One bone mass measurement can predict bone fracture risk for as long as over 10 years or more, but predictive ability of BMD decreases with time. Therefore, cost effectiveness needs to be reviewed to determine the benefits of screening among peri-menopausal women and men. Although bone assessment by quantitative ultra sound (QUS) method by ultrasound can also predict future fractures, only a relatively small number of longitudinal studies have been conducted in the Western countries, and there is no established evidence by means of longitudinal studies among Japanese. It is necessary in Japan to seek such evidence, however, since this method is widely used for an osteoporosis examinations.     

Bisphosphonate treatment prevents hip fractures in 70-79 year old women with osteoporotic vertebral fractures

According to the data of a fracture intervention trial, in women aged 55-80 years with vertebral fractures or osteoporosis diagnosed by bone mineral density measurement, treatment with the bisphosphonate alendronate prevented hip fractures with numbers-needed-to-treat within 5 years of treatment of 46 and 66, respectively. In a large risedronate hip fracture study, this new bisphosphonate only showed a beneficial effect in women aged 70-79 years with moderately severe osteoporosis as judged by femoral neck T-score, when one or more vertebral fractures were present at the start of the treatment. The number-needed-to-treat was 29. However, in women aged over 80 years and who were selected predominantly on the basis of clinical risk factors for hip fracture, no effect was found with this drug on hip fracture rate, suggesting that most were not osteoporotic and/or that the clinical risk factors used did not have the clinical utility in identifying hip fracture risk. Other factors besides osteoporosis may play a more important role in causing hip fracture in this elderly group. Diagnosis of osteoporotic vertebral fractures in women aged 70-79 years is predictive of not only new vertebral fractures but also of hip fractures, and could therefore form an indication for drug treatment.     

The diagnostics of osteoporosis in the evaluation of fracture risk

Osteoporosis is a metabolic bone disease affecting a large portion of the population. In the osteoporotic process, organic and inorganic components on the bone are reduced, bone quality is deteriorated, strength of bone tissue is diminished, thus fracture risk is increasing as a consequence. Knowledge of the disease is essential for all physicians due to the frequency of this disorder. The aim of osteoporosis diagnostics is to discover the disease, to differentiate from other similar disorders, and to estimate fracture risk in order to introduce effective treatment. To carry out this task effectively, beside the proper evaluation of the patient's history, physical examination, osteodensitometry, X-ray and laboratory tests, some new factors revealed recently known to influence fracture risk should also be considered. The purpose of the present review is to summarize most recent data related to the diagnostics of osteoporosis from the view of the everyday practice.     

Osteoporosis in elderly women should always be treated,despite the new professional guideline from the Dutch Institute for Health Care Improvement (CBO)

According to the Dutch Institute for Healthcare Improvement [Dutch acronym: CBO] professional guideline 'Osteoporosis' (second revision), the treatment of osteoporosis should be based on the patient's age because bone loss at an advanced age is thought to be partly physiological. It is recommended that women < 70 years old are treated if the bone mineral density T-score is below -2.5. For women > or = 70 years of age, a lower cut-off point has been chosen, i.e. a Z-score below -1. However, bone strength is dependent on bone mineral density and the fracture risk doubles if the bone mineral density decreases by one standard deviation. Therefore at an advanced age, any bone loss experienced increases the fracture risk, whether or not the mineral loss is physiological. Moreover, most elderly people carry additional risk factors that increase fracture risk. Therefore in women > or = 70 years of age, the treatment of osteoporosis should be considered if the T-score is below -2.5. In this situation, use of the Z-score is not appropriate.     

Prevention and Treatment of Osteoporosis in Postmenopausal Women

Postmenopausal osteoporosis is characterized by an increased rate of bone turnover accompanied by a reduction in bone mineral density (BMD) that results in an increased risk of fracture, especially of the vertebrae, hip, or wrist. Alendronate (Fosamax®, Fosamax Once-Weekly®), an oral bisphosphonate that inhibits osteoclast-mediated bone resorption and modulates bone metabolism, is a first-line therapy for the management of postmenopausal women with, or at risk of developing, osteoporosis.Alendronate produces sustained increases in BMD and reductions in bone turnover from baseline, and reduces the risk of vertebral, hip, wrist, and other fractures in women with postmenopausal osteoporosis. It also prevents bone loss, and reduces the risk of radiographic or clinical vertebral fracture in postmenopausal osteopenia. Provided administration instructions are followed, alendronate is generally well tolerated. Adverse events are usually transient and are associated with the upper gastrointestinal tract (abdominal pain, nausea, acid regurgitation, dyspepsia); moreover, the incidence of these adverse events with alendronate was similar to those with placebo. More serious events (esophagitis, gastric or duodenal ulceration or bleeding) are uncommon. Once-weekly formulations are as effective and as well tolerated as once-daily alendronate in postmenopausal women.Pharmacoeconomic evaluations suggest that alendronate is a viable treatment option in postmenopausal osteoporosis. The reduction in fracture-related healthcare utilization seen with alendronate results in decreased direct costs, including inpatient or long-term care. Markov state-transition models suggest that this could at least partially offset costs incurred with alendronate therapy. Treatment of women with osteoporosis aged 65 years and older, and postmenopausal women with a previous osteoporotic fracture, are cost-effective strategies. Alendronate is also likely to increase quality-adjusted life-years in any postmenopausal women with osteoporosis.In conclusion, clinical and economic data support the use of alendronate in postmenopausal osteoporosis. It effectively reduces bone turnover, increases BMD, and reduces the risk of osteoporotic fracture in postmenopausal women with established osteoporosis, especially older women with a higher risk of fracture. Although its cost effectiveness in postmenopausal women with osteopenia is not clearly established, alendronate is clinically effective in these patients. In addition, it is generally well tolerated when taken as recommended. Consequently, alendronate should be considered a therapy of choice in the prevention and treatment of osteoporosis in postmenopausal women.     

Vitamins and bone health: beyond calcium and vitamin D

Osteoporosis is a major health disorder associated with an increased risk of fracture. Nutrition is among the modifiable factors that influence the risk of osteoporosis and fracture. Calcium and vitamin D play important roles in improving bone mineral density and reducing the risk of fracture. Other vitamins appear to play a role in bone health as well. In this review, the findings of studies that related the intake and/or the status of vitamins other than vitamin D to bone health in animals and humans are summarized. Studies of vitamin A showed inconsistent results. Excessive, as well as insufficient, levels of retinol intake may be associated with compromised bone health. Deficiencies in vitamin B, along with the consequent elevated homocysteine level, are associated with bone loss, decreased bone strength, and increased risk of fracture. Deficiencies in vitamins C, E, and K are also associated with compromised bone health; this effect may be modified by smoking, estrogen use or hormonal therapy after menopause, calcium intake, and vitamin D. These findings highlight the importance of adequate nutrition in preserving bone mass and reducing the risk of osteoporosis and fractures.