Search

ABSTRACTIntroductionDenosumab (Prolia) is a fully human monoclonal antibody against the receptor activator of the nuclear factor kappaB ligand. It is a potent antiresorptive agent that reduces osteoclastogenesis.Areas CoveredDenosumab has been shown to improve bone mineral density and reduce the incidence of new fractures in postmenopausal women and men. It is also used in the treatment of glucocorticoid-induced osteoporosis, as well as for the prevention of bone loss and reduction of fracture risk in men receiving androgen deprivation therapy for non-metastatic prostate cancer and women receiving adjuvant aromatase inhibitor therapy for breast cancer. Initial safety concerns included infections, cancer, skin reactions, cardiovascular disease, hypocalcemia, osteonecrosis of the jaw, and atypical femur fractures; however, further study and experience provide reassurance on these issues. Anecdotal reports have raised concerns about an increased risk of multiple vertebral fractures following discontinuation of denosumab.Expert OpinionAlthough bisphosphonates are often selected as initial therapy for osteoporosis, denosumab may be an appropriate initial therapy in patients at high risk for fracture, including older patients who have difficulty with the dosing requirements of oral bisphosphonates, as well as patients who are intolerant of, unresponsive to, or have contraindications to other therapies. Additional data is needed to address questions regarding treatment duration and discontinuation.

IMPORTANCE: The best approach to identify younger postmenopausal women for osteoporosis screening is uncertain. The Fracture Risk Assessment Tool (FRAX), which includes self-identified racial and ethnic information, and the Osteoporosis Self-assessment Tool (OST), which does not, are risk assessment tools recommended by US Preventive Services Task Force guidelines to identify candidates for bone mineral density (BMD) testing in this age group. OBJECTIVE: To compare the ability of FRAX vs OST to discriminate between younger postmenopausal women who do and do not experience incident fracture during a 10-year follow-up in the 4 racial and ethnic groups specified by FRAX. DESIGN, SETTING, AND PARTICIPANTS: This cohort study of Women’s Health Initiative participants included 67 169 women (baseline age range, 50-64 years) with 10 years of follow-up for major osteoporotic fracture (MOF; including hip, clinical spine, forearm, and shoulder fracture) at 40 US clinical centers. Data were collected from October 1993 to December 2008 and analyzed between May 11, 2022, and February 23, 2023. MAIN OUTCOMES AND MEASURES: Incident MOF and BMD (in a subset of 4607 women) were assessed. The area under the receiver operating characteristic curve (AUC) for FRAX (without BMD information) and OST was calculated within each racial and ethnic category. RESULTS: Among the 67 169 participants, mean (SD) age at baseline was 57.8 (4.1) years. A total of 1486 (2.2%) self-identified as Asian, 5927 (8.8%) as Black, 2545 (3.8%) as Hispanic, and 57 211 (85.2%) as White. During follow-up, 5594 women experienced MOF. For discrimination of MOF, AUC values for FRAX were 0.65 (95% CI, 0.58-0.71) for Asian, 0.55 (95% CI, 0.52-0.59) for Black, 0.61 (95% CI, 0.56-0.65) for Hispanic, and 0.59 (95% CI, 0.58-0.59) for White women. The AUC values for OST were 0.62 (95% CI, 0.56-0.69) for Asian, 0.53 (95% CI, 0.50-0.57) for Black, 0.58 (95% CI, 0.54-0.62) for Hispanic, and 0.55 (95% CI, 0.54-0.56) for White women. For discrimination of femoral neck osteoporosis, AUC values were excellent for OST (range, 0.79 [95% CI, 0.65-0.93] to 0.85 [95% CI, 0.74-0.96]), higher for OST than FRAX (range, 0.72 [95% CI, 0.68-0.75] to 0.74 [95% CI, 0.60-0.88]), and similar in each of the 4 racial and ethnic groups. CONCLUSIONS AND RELEVANCE: These findings suggest that within each racial and ethnic category, the US FRAX and OST have suboptimal performance in discrimination of MOF in younger postmenopausal women. In contrast, for identifying osteoporosis, OST was excellent. The US version of FRAX should not be routinely used to make screening decisions in younger postmenopausal women. Future investigations should improve existing tools or create new approaches to osteoporosis risk assessment for this age group.

Background: The effects of dietary changes on osteoporosis, low bone density, and frequent falls are unestablished. Objective: We assessed the effect of the Women's Health Initiative Dietary Modification low-fat and increased fruit, vegetable, and grain intervention on incident hip, total, and site-specific fractures and self-reported falls, and, in a subset, on bone mineral density (BMD). Design: Postmenopausal women (n = 48,835) aged 50-79 y (18.6% of minority race-ethnicity) were randomly assigned to receive the Dietary Modification intervention (40%, n = 19,541) (daily goal: [less than or equal to] 20% of energy as fat, [greater than or equal to]5 servings of vegetables and fruit, and [greater than or equal to] 6 servings of grains) or to a comparison group that received no dietary changes (60%; n = 29,294). Results: After a mean 8.1 y of follow-up, 215 women in the intervention group and 285 women in the comparison group (annualized rate: 0.14% and 0.12%, respectively) experienced a hip fracture (hazard ratio: 1.12; 95% CI: 0.94, 1.34; P = 0.21). The intervention group (n = 5423; annualized rate: 3.44%) had a lower rate of reporting [greater than or equal to] 2 falls than did the comparison group (n = 8695; annualized rate: 3.67%) (HR: 0.92; 95% CI: 0.89, 0.96; P < 0.01). There was a significant interaction according to hormone therapy use; those in the comparison group receiving hormone therapy had the lowest incidence of hip fracture. In a subset of 3951 women, hip BMD at years 3, 6, and 9 was 0.4-0.5% lower in the intervention group than in the comparison group (P = 0.003). Conclusions: A low-fat and increased fruit, vegetable, and grain diet intervention modestly reduced the risk of multiple falls and slightly lowered hip BMD but did not change the risk of osteoporotic fractures. This trial was registered at clinicaltrials.gov as NCT00000611.

Abstract: This review summarizes and updates data presented at recent annual Southern Medical Association conferences on postmenopausal osteoporosis. As part of any osteoporosis treatment program, it is important to maintain [...]

PURPOSE: To determine the efficacy and safety of cyclical etidronate for up to 7 years in the treatment of postmenopausal osteoporosis and to examine the effects of discontinuing treatment after 2 or 5 years of therapy. PATIENTS AND METHODS: Patients were randomized at entry into the original study in 1986 to blinded treatment for 2 years with either a calcium (placebo) or an intermittent cyclical etidronate regimen, which most patients continued for a third year. Following this phase of the study, patients were enrolled into an open-label, follow-up study (years 4 and 5), during which all patients received cyclical etidronate treatment. In the present double-blind study (years 6 and 7), patients were rerandomized to receive intermittent cyclical therapy with either etidronate or placebo; all patients received calcium. The treatment regimen consisted of 400 mg/day etidronate or placebo for 14 days, followed by 76 days of elemental calcium (500 mg/day); this cycle was repeated approximately 4 times in each year. Of the 193 patients who continued in years 6 and 7 of the study, 93 were randomized to receive cyclical etidronate and 100 were randomized to receive calcium only. For purposes of efficacy analyses, patients were categorized by their total years of cumulative etidronate treatment (7, 5, 4, or 2 years). There were 51, 46, 42, and 54 patients in the 7-, 5-, 4-, and 2-year groups, respectively. Annual assessments included lumbar spine bone mineral density (BMD), as measured by densitometry, and vertebral radiographs. RESULTS: The groups receiving cyclical etidronate during this 2-year study period (7-and 4-year groups) had statistically significant mean percent increases in spinal BMD of 1.8% and 2.2%, respectively (P [is less than] 0.05) at the week 104 observation time. The 5- and 2-year groups, which did not receive etidronate during this period, had mean values of 1.4% and 0.2%, respectively (not significant) at week 104. in the 7-, 5-, 4-, and 2-year groups, the increases in spinal BMD at the end of 7 years were 7.6%, 8.6%, 8.1%, and 3.9%, respectively; these values were statistically significant for all groups compared with original baseline (year 0) (P [is less than] 0.05). BMD of the femur and wrist was maintained throughout the 7-year period. The incidence and rate of vertebral fractures were lowest in patients with the longest exposure to etidronate. Etidronate was well tolerated during the study, with low incidences of gastrointestinal side effects and nonvertebral fractures. CONCLUSIONS: Long-term cyclical etidronate is a safe, effective, and well-tolerated treatment for postmenopausal osteoporosis. Bone mass is maintained for at least 2 years after treatment with etidronate is stopped; however, further gains in spinal bone mass are seen in patients who continue therapy.

PURPOSE: To describe the clinical, histologic, and radiologic findings in patients with diabetic muscular infarction (DMI). MATERIALS AND METHODS:Descriptive case series of 3 patients with DMI and 22 previously reported cases (MEDLINE data base search) in the English literature are presented. RESULTS: Diabetic muscular infarction is usually seen in patients with long-standing insulin-dependent diabetes and multiple end-organ microvascular complications. Two-thirds of patients with DMI are women, with a mean age at presentation of 39 [+ or -] 12 years. The typical clinical presentation includes abrupt onset of thigh pain and tenderness. There is a palpable, painful mass, with swelling and induration of the surrounding tissue without systemic symptoms or signs. The painful lesion persists for weeks, occasionally with exacerbations of symptoms, then spontaneously resolves over several weeks to months. Recurrent episodes are reported in half of the patients. Muscles commonly affected are the vastus lateralis, thigh adductors, and biceps femoris; but calf muscles may be involved as well. Active pathologic changes in the muscle are more sensitively evaluated with T2-weighted sequences on magnetic resonance (MR) imaging, which shows high intensity in involved muscle. Histologic features of DMI consist of large areas of muscle necrosis and edema. Regenerating muscle fibers and lymphocytic interstitial infiltration may be present. CONCLUSION: Diabetic muscular infarction is a rare complication of diabetes mellitus. in most patients, the diagnosis can be made when the characteristic clinical presentation is combined with a typical MR imaging results. Muscle biopsy can be helpful in establishing the diagnosis of DMI, but histologic findings are not specific. Awareness of this syndrome plus MR imaging as the first diagnostic test should lead to the correct diagnosis and shorter hospitalization. Am J Med. 1996; 101:245-250.

PURPOSE: To determine the effect of long-term intermittent cyclic etidronate treatment on spinal bone density and vertebral fracture rates. PATIENTS AND METHODS: Postmenopausal osteoporotic women (n = 423) were randomized initially into a 2-year, double-blind, multicenter study, it was extended to a third year of blinded treatment followed by open-label treatment: 357 patients continued treatment in Year 3 (305 receiving blinded therapy and 52 receiving calcium supplementation) and 277 in Year 4. During Years 1 through 3, patients received double-blind treatment with phosphate (1.0 g) or placebo twice daily for 3 days, etidronate (400 mg) or placebo daily for 14 days, and calcium (500 mg) daily for the remainder of each 91-day treatment cycle. During Year 4, open-label intermittent cyclic etidronate therapy (without preceding phosphate) was administered to all patients. Spinal bone density and vertebral fracture rates were the main outcome measures. RESULTS: During Year 3, etidronate therapy maintained the significant increases in spinal bone mineral density of the first 2 years. Over the 3-year period, proximal femur bone density increased in etidronate-treated patients. Etidronate therapy for 3 years significantly decreased the vertebral fracture rate in patients at higher risk for fracture (low spinal bone density and three or more vertebral fractures at study entry), as compared with nonetidronate treatment (228 versus 412 fractures per 1,000 patient-years, respectively, p

Weight loss is an important aspect of therapy for obese patients with non-insulin-dependent diabetes mellitus (NIDDM). However, blood glucose levels do not always improve after weight loss. Factors that might predict the ability of diet therapy to improve blood glucose levels were assessed in 135 obese patients with NIDDM, who lost at least 9.1 kilograms (kg; 20.0 pounds or lbs.) of body weight. After losing weight, the patients' blood glucose levels were tested and they were subdivided into two groups. Measurements revealed that blood glucose was an average of 7 millimoles per liter in 55 of 135 patients, who were classified as responders; their blood glucose levels had begun to improve after only a slight loss of weight. Eighty of 135 patients were nonresponders; their blood glucose levels measured an average of 18.3 millimoles per liter following weight loss. Improvement in blood glucose levels after weight loss was best predicted by a blood glucose level of 10 millimoles per liter or less after a 2.3 kg (5.0 lbs) and 4.5 kg (9.9 lbs) weight loss. Many patients with NIDDM do not have improved blood glucose levels after weight loss. The effectiveness of diet therapy can be predicted on the basis of blood glucose levels after a 2.3 (5.0 lbs) and 4.5 kg (9.9 lbs) weight loss. It is recommended that patients with NIDDM who remain hyperglycemic (have high blood glucose levels) after losing weight, be considered for treatment with insulin or oral hypoglycemic agents, which lower blood glucose levels. (Consumer Summary produced by Reliance Medical Information, Inc.)

Osteoporosis is less common in men than women; however, the mortality rate associated with major fragility fractures is higher in men. The diagnosis of osteoporosis is established by measurement of bone mineral density or by the presence of a fragility fracture, especially spine or hip fracture. However, many men at high risk of fracture will not meet the T-score criteria for osteoporosis, so fracture risk calculation, with a tool such as FRAX, should be performed. Bone-active agents should be prescribed for men at high risk of fracture to decrease fracture risk, and therapy must be individualized.

IMPORTANCE: Repeated bone mineral density (BMD) testing to screen for osteoporosis requires resources. For patient counseling and optimal resource use, it is important for clinicians to know whether repeated BMD measurement (compared with baseline BMD measurement alone) improves the ability to discriminate between postmenopausal women who will and will not experience a fracture. OBJECTIVE: To assess whether a second BMD measurement approximately 3 years after the initial assessment is associated with improved ability to estimate fracture risk beyond the baseline BMD measurement alone. DESIGN, SETTING, AND PARTICIPANTS: The Women’s Health Initiative is a prospective observational study. Participants in the present cohort study included 7419 women with a mean (SD) follow-up of 12.1 (3.4) years between 1993 and 2010 at 3 US clinical centers. Data analysis was conducted between May 2019 and December 2019. MAIN OUTCOMES AND MEASURES: Incident major osteoporotic fracture (ie, hip, clinical spine, forearm, or shoulder fracture), hip fracture, baseline BMD, and absolute change in BMD were assessed. The area under the receiver operating characteristic curve (AU-ROC) for baseline BMD, absolute change in BMD, and the combination of baseline BMD and change in BMD were calculated to assess incident fracture risk discrimination during follow-up. RESULTS: Of 7419 participants, the mean (SD) age at baseline was 66.1 (7.2) years, the mean (SD) body mass index was 28.7 (6.0), and 1720 (23%) were nonwhite individuals. During the study follow-up (mean [SD] 9.0 [3.5] years after the second BMD measurement), 139 women (1.9%) experienced hip fractures, and 732 women (9.9%) experienced major osteoporotic fracture. In discriminating between women who experience hip fractures and those who do not, AU-ROC values were 0.71 (95% CI, 0.67-0.75) for baseline total hip BMD, 0.61 (95% CI, 0.56-0.65) for change in total hip BMD, and 0.73 (95% CI, 0.69-0.77) for the combination of baseline total hip BMD and change in total hip BMD. Femoral neck and lumbar spine BMD values had similar discrimination for hip fracture. For discrimination of major osteoporotic fracture, AU-ROC values were 0.61 (95% CI, 0.59-0.63) for baseline total hip BMD, 0.53 (95% CI, 0.51-0.55) for change in total hip BMD, and 0.61 (95% CI, 0.59-0.63) for the combination of baseline total hip BMD and change in total hip BMD. Femoral neck and lumbar spine BMD values had similar ability to discriminate between women who experienced major osteoporotic fracture and those who did not. Associations between change in bone density and fracture risk did not differ by subgroup, including diabetes, age, race/ethnicity, body mass index, or baseline BMD T score. CONCLUSIONS AND RELEVANCE: The findings of this study suggest that a second BMD assessment approximately 3 years after the initial measurement was not associated with improved discrimination between women who did and did not experience subsequent hip fracture or major osteoporotic fracture beyond the baseline BMD value alone and should not routinely be performed.

Many aspects of osteoporosis (a condition in which bone mass is gradually reduced), such as diagnosis and evaluation, causes, prevention, and treatment are now at least partially understood. Therefore, primary care physicians need to be aware of the risk factors associated with this disorder. A study in the March 1991 issue of The Journal of Family Practice indicated that risk factors are rarely documented or are documented incompletely; the risk-factor approach, however, may overly complicate the situation. Two terms are described: osteoporosis, a condition of bone mass loss associated with fractures in the absence of trauma; and osteopenia, a condition of low bone mass where no fractures have occurred. Osteopenia is thus the major risk factor for osteoporosis, but accurate prediction of which patients will develop fractures is impossible. The risk factors for osteopenia include the nonremediable ones of ethnicity, advanced age, family history, small frame, and low body weight. Some factors are remediable: cigarette smoking, heavy use of alcohol, a sedentary lifestyle, and the use of certain medications (glucocorticoids, anticonvulsants, thyroid hormones). When decisions concerning estrogen administration (the only currently approved method for preventing osteoporosis) are made, broader issues concerning patients' health should be considered. The drawbacks of estrogen therapy, (endometrial cancer, blood clots, aggravation of fibrocystic breast disease) need to be considered. Patients should be informed regarding the optimal calcium intake. The best approach to evaluating the extent of osteopenia is measurement of bone density, and it may be wise to perform such measurements in all women around the age of menopause. Clinical evaluation does not accurately identify at-risk patients. Techniques of bone density measurement are described. Salmon calcitonin is the only drug now approved for treating established osteoporosis; other agents under consideration are discussed. The condition can only be effectively prevented by using bone densitometry to identify women with osteopenia; many patients cannot be diagnosed by clinical criteria alone. (Consumer Summary produced by Reliance Medical Information, Inc.), Prevention of Osteoporosis: The Role of Primary Physicians There has been a rapid escalation of knowledge about osteoporosis over the past several years. We now have a clear understanding of [...]

Odanacatib, a cathepsin K inhibitor, reduces bone resorption while maintaining bone formation. Previous work has shown that odanacatib increases bone mineral density in postmenopausal women with low bone mass. We aimed to investigate the efficacy and safety of odanacatib to reduce fracture risk in postmenopausal women with osteoporosis.

Conventional hypoparathyroidism treatment with oral calcium and active vitamin D is aimed at correcting hypocalcemia but does not address other physiologic defects caused by PTH deficiency.

Antiresorptive therapy has been associated with osteonecrosis of the jaw (ONJ), an infrequent but potentially serious adverse event.

Several risk factors are important EDITOR--Wilkin argues for broadening the indication for treatment of osteoporosis to 'infirm older people.'[1] There are several problems with the specific case he makes but [...]

(Abstracted from Obstet Gynecol2020;135:1313–1326)Uterine leiomyomas affect up to 80% of reproductive-age women and are the most common benign neoplasm of the uterus. A variety of symptoms occur in approximately half of these women; the most common is heavy menstrual bleeding (HMB), which can result in anemia.

Osteoporosis is a silent condition characterized by reduced bone mass and abnormal bone architecture, with an associated increase in the risk of fractures. It affects approximately 44 million Americans. The [...]

Bone densitometry is routinely used to assess the skeleton in patients who have diseases or conditions that can cause low bone mass. However, there are some areas of controversy related [...]

The Women's Health Initiative (WHI) hormone therapy (HT) trials showed protection against hip and total fractures, but a later observational report suggested loss of benefit and a rebound increased risk after cessation of HT.

* Gonadotropin levels were measured in 65 postmenopausal women admitted to the intensive care unit. Sixteen patients (25%) were hypogonadotropic as measured by luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels of 5 IU/L or less, and only 20 patients (31%) were found to have gonadotropin levels within the expected postmenopausal range ([is greater than or equal to] 30 IU/L). No significant differences in prolactin or free thyroxine levels were found, but the cortisol level was higher and the total thyroxine level lower in the hypogonadotropic group. The patients in the hypogonadotropic group also seemed more seriously ill, with a longer duration of hospitalization, an increased total number of days in the intensive care unit, an increased number of days in the intensive care unit before gonadotropin sampling, a higher incidence of parenteral hyperalimentation, lower serum albumin levels, and higher mortality. Stimulation of the gonadotropin-releasing hormone performed on 10 patients showed a blunted response in patients with baseline LH and FSH levels of 10 IU/L or less. Of 10 patients followed up sequentially, 6 showed a rise in gonadotropin levels that paralleled recovery, 1 died with low gonadotropin levels, and 3 continued to have low gonadotropin levels 17, 34, and 82 days, respectively, after initial screening. Critically ill postmenopausal women may exhibit a marked fall in gonadotropin, LH, and FSH levels. This disease in gonadotropin levels in response to illness is reversible and results from pituitary unresponsiveness to gonadorelin hydrochloride.

To develop an innovative and effective educational intervention to inform patients about the need for osteoporosis treatment and to determine factors associated with its online uptake.

Context:Canagliflozin is a sodium glucose cotransporter 2 inhibitor developed to treat type 2 diabetes mellitus (T2DM).Objective:Our objective is to describe the effects of canagliflozin on bone mineral density (BMD) and bone biomarkers in patients with T2DM.Design:This was a randomized study, consisting of a 26-week, double-blind, placebo-controlled period and a 78-week, double-blind, placebo-controlled extension.Setting:This study was undertaken in 90 centers in 17 countries.Patients:Patients were aged 55–80 years (N = 716) and whose T2DM was inadequately controlled on a stable antihyperglycemic regimen.Interventions:Canagliflozin 100 or 300 mg or placebo were administered once daily.Outcome and Measures:BMD was assessed using dual-energy x-ray absorptiometry at weeks 26, 52, and 104. Bone strength was assessed using quantitative computed tomography and finite element analysis at week 52. Serum collagen type 1 β-carboxy-telopeptide, osteocalcin, and estradiol were assessed at weeks 26 and 52.Results:Canagliflozin doses of 100 and 300 mg were associated with a decrease in total hip BMD over 104 weeks, (placebo-subtracted changes: −0.9% and −1.2%, respectively), but not at other sites measured (femoral neck, lumbar spine, or distal forearm). No meaningful changes in bone strength were observed. At week 52, canagliflozin was associated with an increase in collagen type 1 β-carboxy-telopeptide that was significantly correlated with a reduction in body weight, an increase in osteocalcin, and, in women, a decrease in estradiol.Conclusions:In older patients with T2DM, canagliflozin showed small but significant reductions in total hip BMD and increases in bone formation and resorption biomarkers, due at least in part to weight loss.

Context:Canagliflozin is a sodium glucose cotransporter 2 inhibitor developed to treat type 2 diabetes mellitus (T2DM).Objective:The purpose of this study was to describe the effects of canagliflozin on bone fracture risk.Design and Setting:This was a randomized phase 3 study in patients with T2DM.Patients and Interventions:Canagliflozin doses of 100 and 300 mg were evaluated in the overall population of patients from 9 placebo- and active-controlled studies (N = 10 194), as well as in separate analyses of a single trial enriched with patients with a prior history/risk of cardiovascular disease (ie, the CANagliflozin cardioVascular Assessment Study [CANVAS]; N = 4327) and a pooled population of 8 non-CANVAS studies (N = 5867).Outcome Measures:The incidence of adjudicated fracture adverse events (AEs), fall-related AEs, and volume depletion–related AEs was assessed.Results:The incidence of fractures was similar with canagliflozin (1.7%) and noncanagliflozin (1.5%) in the pooled non-CANVAS studies. In CANVAS, a significant increase in fractures was seen with canagliflozin (4.0%) vs placebo (2.6%) that was balanced between the upper and lower limbs. The incidence of fractures was higher with canagliflozin (2.7%) vs noncanagliflozin (1.9%) in the overall population, which was driven by the increase of fractures in CANVAS. The incidence of reported fall-related AEs was low, but significantly higher with canagliflozin in CANVAS, potentially related to volume depletion–related AEs, but not significantly different in the pooled non-CANVAS studies and the overall population.Conclusions:Fracture risk was increased with canagliflozin treatment, driven by CANVAS patients, who were older, with a prior history/risk of cardiovascular disease, and with lower baseline estimated glomerular filtration rate and higher baseline diuretic use. The increase in fractures may be mediated by falls; however, the cause of increased fracture risk with canagliflozin is unknown.

It's against the law to shout 'fire' in a crowded theater (unless there really is a fire). Recent misleading reports in the lay press of cases of 'atypical' femur fractures [...]

Date of Original Release: June 1, 2004 Term of Approval: 1 Year * Credit Expires: June 1, 2005 Estimated Time for Completion: 1 Hour The following section was designed for [...]

Among the fractures defined as major in FRAX®(hip, upper arm, forearm and clinical vertebral), the percentage of hip fractures is consistent across regions, but that of nonhip fractures varies substantiallyEconomic analyses most often assess spine and hip fractures, but nonvertebral, nonhip fractures are common, lead to twofold increased resource use compared with hip and spine fractures combined, and greatly affect quality of lifeObesity is protective against hip fractures but is associated with an increased risk of fractures of the ankle and lower legThe predictive value of specific risk factors differs by skeletal sites and by risk profile for first and subsequent fracturesRates of treatment with antiosteoporotic drugs fall short of guideline recommendations in women at high risk but are perhaps too frequent in women at low risk

Introduction:Denosumabis a fully human monoclonal antibody against the receptor activator of nuclear factor kappa-B ligand. It is an antiresorptive agent that reduces osteoclastogenesis.Areas covered:This drug evaluation reviews denosumab for use in osteoporosis. Denosumab has been shown to improve bone mineral density (BMD) and to reduce the incidence of new vertebral, hip and nonvertebral fractures in postmenopausal women. It prevents bone loss and reduces vertebral fracture risk in men with nonmetastatic prostate cancer who are receiving androgen deprivation therapy. It has also been shown to improve BMD in men with osteoporosis unrelated to androgen deprivation therapy. Safety concerns include infections, cancer, skin reactions, cardiovascular disease, hypocalcemia, osteonecrosis of the jaw and atypical femur fractures.Expert opinion:Although bisphosphonates are typically preferred as initial therapy for osteoporosis, denosumab could be used as initial therapy in select patients at high risk for fracture, including older patients who have difficulty with the dosing requirements of oral bisphosphonates, patients who are intolerant of or unresponsive to other therapies, and in those with impaired renal function. Additional data is needed to address issues regarding treatment duration and discontinuation, as well as to provide more information regarding denosumab's efficacy and safety.

Bisphosphonates have been widely used in the treatment of osteoporosis with robust data from numerous placebo-controlled trials demonstrating efficacy in fracture risk reduction over 3–5 years of treatment. Although bisphosphonates are generally safe and well tolerated, concerns have emerged about adverse effects related to long-term use. For most patients with osteoporosis, the benefits of treatment outweigh the risks. Because these agents accumulate in bone with some persistent antifracture efficacy after therapy is stopped, it is reasonable to consider a ‘drug holiday.’ There is considerable controversy regarding the optimal duration of therapy and the length of the holiday, both of which should be based on individual assessments of risk and benefit.

OBJECTIVE: Osteoporotic fractures are associated with significant morbidity and mortality particularly among older men. However, there is little information regarding risk factors among this population. The aims of our study were to determine risk factors for osteoporosis and fragility fractures and the predictive value of bone mineral density (BMD) measurements for development of fragility fractures in a cohort of elderly Caucasian and African American men. METHODS: We evaluated 257 men aged 70 years or older for risk factors for osteoporosis and fragility fractures using a detailed questionnaire and BMD assessment. Exclusion criteria included conditions known to cause osteoporosis such as hypogonadism and chronic steroid use, current treatment with bisphosphonates, bilateral hip arthroplasties, and inability to ambulate independently. RESULTS: Age, weight, weight loss, androgen deprivation treatment, duration of use of dairy products, exercise, and fracture within 10 years prior to study entry were associated with osteoporosis (p ≤ 0.05). Fragility fractures were associated with duration of use of dairy products, androgen deprivation treatment, osteoporosis, and history of fracture within 10 years prior to BMD assessment (p ≤ 0.05). There were some differences in risk factors between the Caucasian and African American populations, suggesting that risk factors may vary between ethnic groups. CONCLUSION: Although men with osteoporosis had a higher rate of fractures, the majority of fractures occurred in men with T-scores > –2.5 standard deviations below the mean, suggesting that factors other than BMD are also important in determining risk.

Further analyses from the Women's Health Initiative estrogen trial shows that CEE reduced fracture risk. The fracture reduction at the hip did not differ appreciably among risk strata. These data do not support overall benefit over risk, even in women at highest risk for fracture.

Whether greater treatment‐related changes in BMD result in greater decreases in fracture risk is controversial. We analyzed the relationship between BMD change and nonvertebral fracture risk in postmenopausal osteoporotic women from the risedronate fracture program. Change in BMD did not influence the magnitude of risedronate's effect on nonvertebral fractures; the incidence of nonvertebral fractures was equally low in treated patients whose BMD increased or decreased.Introduction: In untreated patients, low BMD correlates with increased fracture risk. Whether greater increases in BMD induced by anti‐osteoporosis drugs are related to greater decreases in vertebral fracture risk is controversial, and little has been written about the relationship between change in BMD and nonvertebral fracture risk. We analyzed the relationship between BMD change and nonvertebral fracture incidence using individual patient data from postmenopausal osteoporotic women receiving antiresorptive treatment with risedronate.Materials and Methods: This posthoc analysis combined data from three pivotal risedronate fracture endpoint trials. Women received risedronate 2.5 or 5 mg (n= 2561) or placebo (n= 1418) daily for up to 3 years. BMD and nonvertebral fractures confirmed by radiograph (hip, wrist, pelvis, humerus, clavicle, and leg) were assessed periodically over 3 years.Results: The incidence of nonvertebral fractures in risedronate‐treated patients was not different between patients whose spine BMD decreased (7.8%) and those whose spine BMD increased (6.4%; hazard ratio to subgroup of patients who lost BMD [HR], 0.79; 95% CI, 0.50, 1.25) or between those whose femoral neck BMD decreased (7.6%) and those whose femoral neck BMD increased (7.5%; HR, 0.93; 95% CI, 0.68, 1.28). The changes in lumbar spine and femoral neck BMD explained only 12% (95% CI, 2%, 21%; p= 0.014) and 7% (95% CI, 2%, 13%; p= 0.005), respectively, of risedronate's nonvertebral fracture efficacy.Conclusions: For patients treated with risedronate, changes in BMD as measured by DXA do not predict the degree of reduction in nonvertebral fractures.

Accurate radiographic diagnosis of vertebral fractures is important. This multicenter, multinational study assessed radiographic diagnoses of vertebral fracture in 2451 postmenopausal women with osteoporosis. Comparison between local and central readings yielded a false‐negative rate of 34%. Underdiagnosis of vertebral fracture is a worldwide problem.

ABSTRACTObjectives:BONE (oral iBandronate Osteoporosis vertebral fracture trial in North America and Europe) determined whether less frequent dosing of ibandronate (dose-free interval > 2 months) provided similar antifracture efficacy to daily dosing. As osteoporosis medications must be effective across different populations, an additional objective of BONE was to investigate and report the effect of oral ibandronate in North American and European women, as described here.Patients and methods:BONE was a randomized, double-blind, placebo-controlled, fracture-prevention study in 2946 postmenopausal women (age 55 years−80 years; ≥ 5 years since menopause) with osteoporosis (low lumbar spine bone mineral density and one to four prevalent vertebral fractures [T4−L4]). Participants received daily calcium (500 mg) and vitamin D (400 IU) plus either placebo, oral daily ibandronate (2.5 mg) or oral intermittent ibandronate (20 mg every other day for 12 doses every 3 months). The efficacy and tolerability of ibandronate were assessed independently in both North American and European populations.Results:Consistent, significant efficacy was observed in the North American (new vertebral fracture risk reduction: 60% and 54% with daily and intermittent ibandronate, respectively) and European patient populations (50% and 48%, respectively). Both ibandronate regimens also significantly reduced the incidence of new, worsening, and acute clinical, vertebral fractures. Daily and intermittent ibandronate significantly increased bone density at the spine in both North American (5.4% and 4.4% vs. baseline with daily and intermittent ibandronate, respectively) and European (7.1% and 6.3% vs. baseline, respectively) populations. Significant increases were also observed for total hip bone density (2.6% and 3.7% vs. baseline for daily, and 2.5% and 3.1% for intermittent; North American and European populations, respectively). Comparable, significant decreases in biochemical markers of bone turnover (reductions in urinary excretion of C-telopeptide levels of 53.5% and 67.1% vs. baseline for daily, and 50.0% and 53.8% for intermittent; North American and European populations, respectively) were also observed in both populations ( p< 0.004 for all cited measurements in each ibandronate group vs. placebo). Oral ibandronate was well tolerated in both North American and European patients, with a safety profile similar to placebo.Conclusions:Oral ibandronate, administered daily or intermittently, effectively reduced vertebral fracture risk in North American and European women with postmenopausal osteoporosis. These results demonstrate the efficacy of ibandronate administered with extended dose-free intervals, regardless of patients’ geographical origin. Research investigating other less frequent ibandronate regimens, such as once-monthly oral administration, is underway.

Determine the effect of raloxifene or estrogen, as compared with placebo, on the reporting of urinary incontinence in postmenopausal women participating in an osteoporosis prevention trial.

SUMMARYObjective:Postmenopausal osteoporotic women with pre-existing or new incident vertebral fractures are at high risk for future fracture, so prompt treatment is warranted. Risedronate has been shown to reduce the incidence of radiographically-defined vertebral fractures by approximately two-thirds within 1 year.Research design:This study examined the effects of risedronate treatment on the time course of the reduction in the risk of clinical vertebral fractures (i.e., symptomatic fractures), on the risk of moderate-to-severe radiographic vertebral fractures, and on height.Results:In 2442 postmenopausal women with prevalent vertebral fractures from the Vertebral Efficacy with Risedronate Therapy (VERT) studies who received either risedronate 5 mg or placebo, daily risedronate reduced the risk of clinical vertebral fractures within 6 months (RR 0.08, 95 CI 0.01-0.63), and by 69 at 1 year (RR 0.31, 95 CI 0.12, 0.78). At 1 year, risedronate also reduced the risk of moderate-to-severe radiographically-defined vertebral fractures by 71 (RR 0.29 95 CI 0.16, 0.54). Height loss was attenuated with treatment, most notably in patients who experienced new vertebral fractures, with a median difference of 0.73 cm compared with subjects receiving placebo ( p 0.005).Conclusion:Risedronate reduces the risk of clinical vertebral fractures in postmenopausal women with osteoporosis within 6 months of commencing treatment.