Pathophysiology Of Osteoporosis Research Articles

Searching for the Molecular Pathways Regulating Bone Mineral Density in the Proteome and RNA Interference Era

Osteoporosis is a polygenic disorder associated with low bone mineral density and deterioration of bone microarchitecture with increased chance of bone fractures. Although bone matrix mineralization and osteoporosis are closely related, the mineralization of bone matrix is almost a forgotten aspect in osteoporosis research. The complex processes of bone matrix mineralization and bone remodeling are tightly regulated by several transcription factors and signal transduction pathways. However, signal transduction pathways occurring at a protein level that depends not only on mRNA transcriptional regulation but also on a multitude of translational and posttranslational controls. Furthermore, proteomics allow a discerning view of complex molecular pathways, provides an efficient method to determine protein candidates, and elucidates signal transduction pathways that regulate bone mineral density and accelerates the discovery of osteoporosis causative genes. RNA interference is a powerful tool for rapid analysis of gene functions. Therefore, strategies to combine proteomics with RNA interference and transgenic RNAi would greatly improve the efficiency of gene discovery and divulge the molecular pathways involved in osteoporosis pathophysiology. In this review, current methods employed to identify genes involved in osteoporosis, which include linkage analysis, candidate gene association studies, genome wide association studies, transcriptome microarray, and proteomics are evaluated, and a new strategy is proposed.

Effect of Potassium Citrate on Bone Density, Microarchitecture, and Fracture Risk in Healthy Older Adults without Osteoporosis: A Randomized Controlled Trial

The acid load imposed by a modern diet may play an important role in the pathophysiology of osteoporosis. Our objective was to evaluate the skeletal efficacy and safety and the effect on fracture prediction of K-citrate to neutralize diet-induced acid loads. We conducted a randomized, double-blind, placebo-controlled trial at a teaching hospital. Subjects included 201 elderly (>65 yr old) healthy men and women (t-score of -0.6 at lumbar spine). Intervention was 60 mEq of K-citrate daily or placebo by mouth. All subjects received calcium and vitamin D. The primary outcome was change in areal bone mineral density (aBMD) at the lumbar spine by dual-energy x-ray absorptiometry after 24 months. Secondary endpoints included changes in volumetric density and microarchitectural parameters by high-resolution peripheral quantitative computed tomography in both radii and both tibiae and fracture risk assessment by FRAX (Switzerland). K-citrate increased aBMD at lumbar spine from baseline by 1.7 ± 1.5% [95% confidence interval (CI) = 1.0-2.3, P < 0.001] net of placebo after 24 months. High-resolution peripheral quantitative computed tomography-measured trabecular densities increased at nondominant tibia (1.3 ± 1.3%, CI = 0.7-1.9, P < 0.001) and nondominant radius (2.0 ± 2.0%, CI = 1.4-2.7, P < 0.001). At nondominant radius, trabecular bone volume/tissue volume increased by 0.9 ± 0.8%, (CI = 0.1-1.7), trabecular thickness by 1.5 ± 1.6% (CI = 0.7-2.3), and trabecular number by 1.9 ± 1.8% (CI = 0.7-3.1, for all, P < 0.05). K-citrate diminished fracture prediction score by FRAX significantly in both sexes. Among a group of healthy elderly persons without osteoporosis, treatment with K-citrate for 24 months resulted in a significant increase in aBMD and volumetric BMD at several sites tested, while also improving bone microarchitecture. Based on the effect on fracture prediction, an effect on future fractures by K-citrate is possible.

The Skeleton and the Sympathetic Nervous System: It's about Time!

In this edition of the JCEM, Farr et al. (1) explore the role of the sympathetic nervous system (SNS) in the pathophysiology of osteoporosis. They hypothesized that sympathetic tone would be increased in postmenopausal women and that this rise would be associated with a lower trabecular bone volume fraction in the radius, as well as decreased serum amino-terminal propeptide of type I procollagen (PINP), a marker of bone formation and osteopontin (1). To test their hypothesis, the investigators employed a well-recognized, albeit invasive method to measure sympathetic tone, i.e. intraarterial catheterization and microneurography of the peroneal nerve (2). Quantification of sympathetic activity was regressed against parameters of skeletal microarchitecture measured by high-resolution peripheral quantitative computed tomography (HRpQCT) as well as by indices of bone turnover; the results were then adjusted for age because both pre- and postmenopausal women were analyzed. Their results point to a potentially important inverse relationship between SNS output and trabecular bone mass in the radius, although not in the tibia, particularly in postmenopausal women (1). Cautiously, the authors call for more studies to definitively assess the importance of the SNS in modulating bone turnover.

Osteoporosis and heart failure

Over recent years there has been an increased interest in osteoporosis as a comorbidity with heart failure, as it is also associated with lifestyle factors relating to cardiovascular disease. There is clear evidence of a correlation between fracture risk and heart failure. Heart failure patients are a vulnerable population for developing osteoporosis; they are predominantly older people, often with existing comorbidities (for example diabetes and renal impairment) and have reduced exercise capacity as a result of the condition. Additionally there are the physiological and pharmacological implications of the condition including high levels of aldosterone and the effects of loop diuretics on calcium levels. It is therefore important that this increased risk is recognised and patients assessed accordingly. The review article outlines the pathophysiology of osteoporosis, identifies the prevalence of the condition in male and female heart failure populations, indicates the typology of heart failure patients likely to develop this problem, and concludes with recommendations for nurses working with patients whose risk should be assessed.

Osteoporosis—a risk factor for cardiovascular disease?

Osteoporosis is a serious health problem worldwide that is associated with an increased risk of fractures and mortality. Vascular calcification is a well-defined independent risk factor for cardiovascular disease (CVD) and mortality. Major advances in our understanding of the pathophysiology of osteoporosis and vascular calcification indicate that these two processes share common pathogenetic mechanisms. Multiple factors including proteins (such as bone morphogenetic proteins, receptor activator of nuclear factor κB ligand, osteoprotegerin, matrix Gla protein and cathepsins), parathyroid hormone, phosphate, oxidized lipids and vitamins D and K are implicated in both bone and vascular metabolism, illustrating the interaction of these two, seemingly unrelated, conditions. Many clinical studies have now confirmed the correlation between osteoporosis and vascular calcification as well as the increased risk of CVD in patients with osteoporosis. Here, we explore the proposed mechanistic similarities between osteoporosis and vascular calcification and present an overview of the clinical data that support the interaction between these conditions.

The future of osteoporosis treatment - a research update

Osteoporosis is characterised by a progressive loss of bone mass and microarchitecture which leads to increased fracture risk. Some of the drugs available to date have shown reductions in vertebral and non-vertebral fracture risk. However, in the ageing population of industrialised countries, still more fractures happen today than are avoided, which highlights the large medical need for new treatment options, models, and strategies. Recent insights into bone biology, have led to a better understanding of bone cell functions and crosstalk between osteoblasts, osteoclasts, and osteocytes at the molecular level. In the future, the armamentarium against osteoporotic fractures will likely be enriched by (1.) new bone anabolic substances such as antibodies directed against the endogenous inhibitors of bone formation sclerostin and dickkopf-1, PTH and PTHrp analogues, and possibly calcilytics; (2.) new inhibitors of bone resorption such as cathepsin K inhibitors which may suppress osteoclast function without impairing osteoclast viability and thus maintain bone formation by preserving the osteoclast-osteoblast crosstalk, and denosumab, an already widely available antibody against RANKL which inhibits osteoclast formation, function, and survival; and (3.) new therapeutic strategies based on an extended understanding of the pathophysiology of osteoporosis which may include sequential therapies with two or more bone active substances aimed at optimising the management of bone capital acquired during adolescence and maintained during adulthood in terms of both quantity and quality. Finally, one of the future challenges will be to identify those patients and patient populations expected to benefit the most from a given drug therapy or regimen. The WHO fracture risk assessment tool FRAX® and improved access to bone mineral density measurements by DXA will play a key role in this regard.

Curculigoside isolated from &amp;lt;italic&amp;gt;Curculigo orchioides&amp;lt;/italic&amp;gt; prevents hydrogen peroxide-induced dysfunction and oxidative damage in calvarial osteoblasts

Reactive oxygen species (ROS), including H(2)O(2), play a critical role in the pathophysiology of osteoporosis. Therefore, agents or antioxidants that can inhibit ROS production have a high clinical value in the treatment of osteoporosis. Curculigoside (CUR), one of the main bioactive phenolic compounds isolated from the rhizome of Curculigo orchioides Gaertn., is reported to have potent antioxidant and anti-osteoporotic properties. However, there is no direct evidence to link the antioxidant capacity of CUR with the observed anti-osteoporotic effect, and relevant molecular mechanisms remain unclear. Therefore, we investigated the protective effects of CUR against oxidative stress in calvarial osteoblasts and discussed the related mechanisms. It was found that osteoblast viability decreased significantly after 48-h exposure to 400 μM of H(2)O(2), compared with vehicle-treated cells, and the cytotoxic effect of H(2)O(2) was reversed significantly when pretreated with 0.1-10 μM of CUR (P< 0.05). Pretreatment with 0.1-10 μM of CUR decreased ROS production and lipid peroxidation, and increased the activities of antioxidant enzymes, such as superoxide dismutase and glutathione peroxidase in osteoblasts induced by H(2)O(2). In addition, H(2)O(2)-induced reduction of differentiation markers such as alkaline phosphatase, calcium deposition, and Runx2 level was significantly recovered in the presence of CUR. CUR also reversed H(2)O(2)-induced stimulation of extracellular signal-regulated kinase 1/2, and nuclear factor-κB signaling and the inhibition of p38 mitogen-activated protein kinase activation. These results provide new insights into the osteoblast-protective mechanisms of CUR through reducing the production of ROS, suggesting that CUR may be developed as a bio-safe agent for the prevention and treatment of osteoporosis and other bone-related human diseases.

DPP4 inhibition alters the pathophysiology of osteoporosis

DPP4 inhibition alters the pathophysiology of osteoporosis

T cell‐mediated increased osteoclast formation from peripheral blood as a mechanism for crohn's disease‐associated bone loss

The pathophysiology of osteoporosis in patients with Crohn's disease (CD) is still not completely elucidated. In this study, we evaluated osteoclastogenesis from peripheral blood cells of CD patients and studied the role of lymphocytes and inflammatory cytokines in this process. Peripheral blood mononuclear cells from seven patients with quiescent CD and matched healthy controls were isolated, and separated into T cells, B cells, and a T- and B-cell depleted fraction. In various culture combinations, osteoclast formation in the absence of the osteoclastogenic factors RANKL and M-CSF was assessed by scoring the number of tartrate-resistant acid phosphatase (TRACP) positive multinucleated cells (MNCs). Cytokine levels in culture supernatants were measured. Formation of heterogeneous cell clusters in culture was noticed; a process that was inhibited by anti-LFA-1. In CD cultures, mean cluster area was up to threefold higher than in control cultures, and shown to be induced by T cells. Over tenfold higher numbers of TRACP(+) MNCs were found in CD cultures, but exclusively in cultures containing T cells. Formation of cell clusters correlated strongly with formation of TRACP(+) MNCs. Both cell cluster formation and osteoclast formation were related to IL-17 levels in vitro. In conclusion, osteoclastogenesis, preceded by cell cluster formation, is T cell-mediated and increased in patients with quiescent CD. Our findings suggest heterotypic interactions between osteoclast precursors and T cells to be a triggering step in osteoclast formation in CD. Furthermore, our results propose a possible role for IL-17 in osteoclastogenesis in CD patients, and as such in CD-associated bone loss.

Osteoporosis and Vitamin D Deficiency in HIV-Positive Patients

Objective: To review the epidemiology and pathophysiology of osteoporosis in patients with HIV infection and discuss vitamin D deficiency and the treatment of HIV-positive patients with osteoporosis. Data Sources: A search of PubMed (1980–June 2011) was conducted using the terms osteoporosis, HIV, vitamin D deficiency, and treatment. Study Selection and Data Extraction: Epidemiologic studies, clinical trials, and meta-analyses published in English were included. A manual review of the bibliographies of available literature was conducted and relevant articles were reviewed for inclusion. Data Synthesis: Patients with HIV infection are living longer with the use of potent antiretroviral therapy (ART) and are at increased risk for osteoporosis. Several studies have shown that HIV infection can affect bone health and increase the risk for osteoporosis. In addition, ART, and tenofovir in particular, may affect bone turnover. Studies and meta-analyses have shown an increased prevalence of osteopenia and osteoporosis in HIV-positive patients compared to noninfected controls. Recent reports also show increased prevalence of fractures and low vitamin D concentrations in HIV-positive patients. Osteoporosis treatments used in patients with HIV infection are similar to treatments for noninfected patients. HIV-positive patients should be monitored and treated to prevent the progression and complications of osteoporosis. Conclusions: HIV-positive patients are at increased risk for osteoporosis and vitamin D deficiency due to disease and treatment influences on bone health. These patients should be identified and treated to prevent the morbidity and mortality associated with osteoporosis.

Osteoporosis Update

Osteoporosis is a chronic disease that is estimated to affect more than 75 million people worldwide. The US Department of Health and Human Services projects that the disease will impact more than 10 million women by 2020 if efforts to prevent it are ineffective. This article provides an overview of the pathophysiology of osteoporosis, prevention measures, and an update of the US Food and Drug Administration-approved medications that are used in the treatment of this widespread disease. The current literature on the pathology, risks, and treatment of osteoporosis was reviewed. Studies providing the evidence for best practices are included in the following sections: prevention, diagnosis, and treatment of osteoporosis. Current national standards for diagnosis and treatment are highlighted. Bisphosphonates continue to be the most popular and widely used pharmacologic treatment for osteoporosis. However, when bisphosphonates are contraindicated or cause side effects so serious that it is not possible for some women to use them, alternative pharmacologic treatments and forms of dosing are available. When lifestyle and dietary modifications are insufficient to offset a diagnosis of osteoporosis, there are a variety of pharmaceutical options available that will provide safe and effective protection against fracture due to osteoporosis.

Development and aging of bone in the female life cycle

In Japan, where the society is fast aging at an unprecedented pace, osteoporosis is estimated to affect more than 15 million individuals, thus representing a "common" disease, which exactly meets the definition of a lifestyle-related disease. As osteoporosis has a predominantly female prevalence and bone accounts for the most marked gender difference all organs commonly affected in males and females alike, to have an understanding of the development and aging of bone in women represents an urgent task toward gaining a better understanding of the pathophysiology of osteoporosis affecting them as well as its clinical stages. In this context, the benefit of ensuring bone health has been identified as maintenance of ADL/QOL in the elderly as well as prevention of osteoporotic fractures which lead to affected individuals becoming bed-ridden and requiring nursing care.

Peripheral Blood Monocyte-expressed ANXA2 Gene is Involved in Pathogenesis of Osteoporosis in Humans

Low bone mineral density (BMD) is a risk factor of osteoporosis and has strong genetic determination. Genes influencing BMD and fundamental mechanisms leading to osteoporosis have yet to be fully determined. Peripheral blood monocytes (PBM) are potential osteoclast precursors, which could access to bone resorption surfaces and differentiate into osteoclasts to resorb bone. Herein, we attempted to identify osteoporosis susceptibility gene(s) and characterize their function(s), through an initial proteomics discovery study on PBM in vivo, and multiscale validation studies in vivo and in vitro. Utilizing the quantitative proteomics methodology LC-nano-ESI-MS(E), we discovered that a novel protein, i.e. ANXA2, was up-regulated twofold in PBM in vivo in Caucasians with extremely low BMD (cases) versus those with extremely high BMD (controls) (n = 28, p < 0.05). ANXA2 gene up-regulation in low BMD subjects was replicated at the mRNA level in PBM in vivo in a second and independent case-control sample (n = 80, p < 0.05). At the DNA level, we found that SNPs in the ANXA2 gene were associated with BMD variation in a 3(rd) and independent case-control sample (n = 44, p < 0.05), as well as in a random population sample (n = 997, p < 0.05). The above integrative evidence strongly supports the concept that ANXA2 is involved in the pathogenesis of osteoporosis in humans. Through a follow-up cellular functional study, we found that ANXA2 protein significantly promoted monocyte migration across an endothelial barrier in vitro (p < 0.001). Thus, elevated ANXA2 protein expression level, as detected in low BMD subjects, probably stimulates more PBM migration through the blood vessel walls to bone resorption surfaces in vivo, where they differentiate into higher number of osteoclasts and resorb bone at higher rates, thereby decreasing BMD. In conclusion, this study identified a novel osteoporosis susceptibility gene ANXA2, and suggested a novel pathophysiological mechanism, mediated by ANXA2, for osteoporosis in humans.

Successes in Understanding Pathophysiology of Osteoporosis

Successes in Understanding Pathophysiology of Osteoporosis

Osteoporosis senil: una actualización

Knowledge of the mechanisms underlying the development of osteoporosis in the elderly has advanced greatly in the past few years. After an initial sudden loss of bone mineral mass in the peri-menopausal period there follows a more progressive and gradual loss that has also been seen in men. This initial drop in bone mass is due to a significant increase in bone resorption. There is also a significant reduction in bone formation with age that is mainly due to osteoblastogenesis in the bone marrow passing to a second plane, transferring its main role to adipogenesis. In this article, the latest evidence on the pathophysiology of senile osteoporosis is reviewed, highlighting the mechanisms of action of available treatments. Potential future treatments are also considered, which include new therapeutic approaches based on the pathophysiology of osteoporosis in the elderly, mainly on the potential reversibility of the adipogenesis.

Denosumab

Denosumab (Prolia®) [1, 2] offers a new approach in the treatment of osteoporosis. It decreases bone resorption by inhibiting osteoclast formation, function and survival. The current indication covers osteoporosis in postmenopausal women at increased risk of fracture and men receiving hormonal therapy for prostate cancer. Osteoporosis is characterized by an imbalance between bone formation and bone resorption. The latter process is performed by osteoclasts and occurs at a higher rate in osteoporosis. Receptor activator of nuclear factor-κB ligand (RANKL) is an essential factor in osteoclast differentiation, activation and survival. RANKL, a member of the tumour necrosis factor (TNF) superfamily, is expressed on the osteoblast membrane and binds to receptor activator of nuclear factor-κB (RANK, the receptor) on the osteoclast membrane (Figure 1). Osteoprotegerin (OPG) is the endogenous regulator of this RANKL-mediated activation of osteoclasts. OPG is a soluble RANKL-binding protein that binds RANKL, preventing it from combining with RANK on the osteoclast membrane and thus inhibiting its action. RANK is a membrane-bound, TNF-like receptor that recognizes RANKL through direct cell-to-cell interaction with osteoblasts. Pathophysiology of osteoporosis. Osteoporosis is characterized by a higher rate of bone resorption compared with bone formation. Bone resorption requires differentiation and activation of osteoclasts. Receptor activator of nuclear factor-κB ligand (RANKL) is an essential, stimulating factor in this regulatory process. Binding of RANKL (expressed on the osteoblast membrane) to its receptor activator of nuclear factor-κB (RANK, the receptor) in the osteoclast membrane triggers osteoclast activation and leads to bone resorption. Osteoprotegerin (OPG) is a soluble RANKL receptor and thus acts as an endogenous inhibitor of this RANKL-mediated activation process Denosumab is a human monoclonal IgG2 antibody that binds RANKL with high affinity and specificity, preventing interaction with RANK on the osteoclast membrane (Figure 2). Thus, it mimics endogenous OPG. By attaching to and blocking RANKL, denosumab inhibits osteoclast differentiation, activation and survival. This favours bone formation over bone resorption, increasing bone mass and reducing the risk of fractures [3]. Mechanism of action of denosumab. Denosumab binds to RANKL thereby preventing interaction with RANK on the osteoclast membrane. By attaching to and blocking RANKL, denosumab inhibits osteoclast differentiation and activation. This mechanism of action decreases bone resorption which leads to improved bone density Denosumab is administered once every 6 months as a 60-mg subcutaneous injection. During treatment, calcium and vitamin D supplementation is important. Hypocalcaemia is not a concern during denosumab therapy when patients are adequately supplemented with calcium and vitamin D. Patients with hypocalcaemia and/or chronic kidney disease may develop symptomatic hypocalcaemia upon treatment with denosumab. Therefore, hypocalcaemia should be corrected before therapy and serum calcium concentration monitored. A dental check and treatment if needed may be advised before starting treatment because of a risk of osteonecrosis of the jaw. Because RANKL also has a function in the immune system denosumab could adversely influence infections of the urinary and upper respiratory tracts. Cataracts were observed in men receiving treatment for prostate cancer but a mechanism has not been elucidated and the findings may be coincidental. The development and progression of cataracts will be studied prospectively in planned clinical studies [4].

Insulin-like growth factor-1 in correlation with bone mineral density among Egyptian adolescents with type 1 diabetes mellitus

Diabetes is associated with alterations in bone health in children and adolescents. The natural history and etiopathogenesis of osteoporosis in type 1 diabetes is not clear. This study was designed primarily to estimate the prevalence of osteoporosis in a sample of type 1 diabetic adolescents and to asses the level of IGF-I and its association with bone mineral density. A total of 60 type 1 diabetic patients and 40 healthy controls aged 13 to 18 years participated in the study. DEXA scan was performed in patients, serum IGF-I, urinary albumin excretion, serum calcium, phosphorus and serum alkaline phosphatase were assessed in both patients and controls. Our results revealed that 50% of our patients have impaired BMD Z score (−2.10 to −1.20), diabetic cases showed significantly lower mean IGF-I when compared to control group (P < 0.0001) and there was positive correlation between BMD and serum level of IGF-I (r = 0.66, P < 0.0001) and not with disease duration, insulin dose, HbA1c and serum metabolic bone markers. Diabetic osteopenic patients had significantly lower mean weight, height and BMI than diabetic non-osteopenic patients (P < 0.0001, P < 0.0001, P < 0.001 respectively). Moreover, age at menarche in diabetic osteopenic females is significantly delayed than non-osteopenic (P = 0.02), a higher frequency of smoking in diabetic osteopenic was observed (p < 0.0001). Impairment of bone mineral density was identified in Egyptian adolescences with T1DM. Lower serum IGF-I levels correlates with decreased mineralization, which suggests its prominent role in the pathophysiology of osteoporosis.

Use of In Vivo Gene Expression of Isolated Bone Marrow Mesenchymal Stromal Cells to Study the Pathophysiology of Osteoporosis in Patients With Severe Thalassemia

We compared osteoblast differentiation gene expressions in the isolated CD105 mesenchymal stromal cells from bone marrow in 10 patients with severe thalassemia and 12 normal donor controls. The fold expressions of osteoblast differentiation genes of CD105 cells from patients with thalassemia were lower than those of normal donors but increased after being cultured in Dulbecco's modified Eagle's medium with 10% fetal calf serum. Moreover, the fold expressions of these genes of CD105 cells from normal donors when cultured with 10% pooled serum of patients with thalassemia were lower than when cultured with 10% pooled serum of normal donors. We have also presented the evidence of reversible suppressed expression of these genes in CD105cells from patients with thalassemia when cultured in pooled serum of normal donors. Moreover, healthy donor CD105 cells exhibited lower expression of these genes when cultured in pooled serum of patients with thalassemia compared with pooled serum of normal donors indicating the existence of circulating factors in thalassemic serum impairing the differentiation of mesenchymal stromal cells to osteoblasts.

Oxytocin and bone remodelling: Relationships with neuropituitary hormones, bone status and body composition

Purpose There is growing evidence that oxytocin, which regulates appetite, plays a role in bone remodelling and improves osteoporosis. We previously showed a significant decrease in circulating oxytocin levels in postmenopausal osteoporotic women compared to healthy controls. However, factors involved in the pathophysiology of osteoporosis, such as estrogens and leptin, are known to regulate oxytocin secretion. Herein, we evaluated the relationships between oxytocin and other hormonal factors known to regulate bone remodeling and body composition in postmenopausal osteoporotic women, compared to healthy controls. Methods In 20 postmenopausal women with severe osteoporosis compared to 16 healthy controls, we measured serum levels of oxytocin, high sensitive estradiol, testosterone, FSH, LH, SHBG, TSH, osteocalcin, serum type I collagen carboxy-terminal telopeptide, leptin. Bone mineral density and body composition were also measured with DXA. Results Osteoporotic women had significantly lower oxytocin, leptin and LH serum levels and higher CTX and SHBG; all other biological parameters were similar in both groups. Fat mass and lean mass were significantly decreased in osteoporotic women. Oxytocin serum levels were significantly correlated to bone mineral density but not to any other measured parameter, including leptin, estradiol and age. In a logistic regression analysis, osteoporosis remained significantly correlated to oxytocin, regardless of age. Conclusions Low oxytocin serum levels appeared to be associated with severe osteoporosis, independently of other factors associated with osteoporosis or known to regulate oxytocin serum levels, such as estradiol or leptin, reinforcing the concept that oxytocin may be involved in the pathophysiology of postmenopausal osteoporosis.

Sex and Gender Considerations in Male Patients With Osteoporosis

Osteoporosis remains underrecognized and undertreated in both men and women, but men who sustain fragility fractures experience greater morbidity and mortality. While men exhibit advanced comorbidity at the time of hip fracture presentation, there are distinct sex- and gender-specific factors related to the pathophysiology and treatment of osteoporosis that further influence morbidity and mortality. With a selective review of the literature, we evaluated sex- and gender-based differences contributing to increased morbidity and mortality in men with osteoporosis. WHERE ARE WE NOW?: Sex-specific differences in bone biology and morphology may affect the pathophysiology of osteoporosis, choice of pharmacotherapy, and surgical implant selection. Additionally, estrogen metabolism may play a key role in both fracture prevention and healing. Gender-based differences in recommendations for screening and prevention between men and women may influence the severity at which osteoporosis is recognized. Primary, secondary, and tertiary prevention efforts in men lag behind those of women. This may be due to a lack of consensus regarding screening guidelines for osteoporosis in men but may be attributed to lack of awareness in the physician and patient about osteoporosis and its potentially debilitating consequences. WHERE DO WE NEED TO GO?: These disparities are a call to action for healthcare providers to raise awareness for early prevention and treatment of this potentially debilitating disease, particularly in men. HOW DO WE GET THERE?: Continued prospective research on the differences between men and women diagnosed with osteoporosis is needed, as well as sex-specific stratification of data in all studies on osteoporosis.