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.     

A method for determining the grade of osteoporosis based on risk factors in postmenopausal women

The aim of this study was to determine whether the probability of osteoporosis and osteopenia was affected by the risk factors, physical examination findings, or radiological investigations such as spinal X-rays in postmenopausal women. We assessed risk factors such as use of hormone replacement therapy, physical activity level, calcium intake, smoking, caffeine consumption, long-term immobilization, previous history of fracture, family history of fracture, presence of certain systemic diseases (hyperthyroidism or hyperparathyroidism), or use of medications (corticosteroids or others), physical examinations, and presence of vertebral fractures on spinal X-rays. Patients bone mineral density (BMD) was evaluated using dual energy X-ray absorptiometry (DXA) in the lumbar spine, and we compared the risk factors between osteopenic and osteoporotic women according to DXA. We evaluated 235 postmenopausal women who attended our osteoporosis outpatient clinic. Those patients were divided into two groups as either osteopenic (n=67, mean age: 63.1 years) or osteoporotic (n=168, mean age: 66.2 years) according to WHO criteria. The lumbar spinal (L1–L2) T-score values were –1.5±0.6 and –3.1±0.6 in osteopenic and osteoporotic groups, respectively. There were significant differences between the two groups in terms of mean age and lumbar BMD (p=0.009 and p<0.001, respectively). We also observed that vertebral tenderness on palpation, back pain, and existing vertebral fracture (fx) were significantly different between the osteopenic and osteoporotic groups (p<0.05). As a result of the statistical analysis, we found an equation to determine osteopenic and osteoporotic women by using those four factors (age, vertebral tenderness on palpation, back pain, and existing vertebral fx) in multivariate stepwise logistic regression. The equation is as follows: (DXA) = –2.9024 + 0.044 (age in year) + 0.819 (vertebral fx) + 0.877 (pain) + 1.136 (vertebral tenderness). We can estimate whether a postmenopausal woman is osteopenic or osteoporotic based on these risk factors by using the stepwise logistic regression equation.     

Osteoporosis: strategies for prevention and management

Osteoporosis is a serious public health issue, affecting up to 1 in 2 women and 1 in 5 men over the age of 50 years. The common osteoporotic fractures occur at the spine, wrist and hip. For the patient affected by osteoporosis, these fractures are associated with significant morbidity and, in the case of hip and spine fractures, an excess mortality. The treatment of osteoporotic fractures is also associated with a significant healthcare cost for society. Currently, measurement of bone mineral density using dual energy X-ray absorptiometry is the gold standard for the diagnosis of osteoporosis. In the future, however, assessment of fracture risk will be based on algorithms incorporating clinical risk factors and bone density measurements, where appropriate. The goal of treatment is to reduce the risk of future fracture. Patients at high risk for fracture should be assessed and screened to exclude secondary causes for osteoporosis. Bisphosphonates (alendronate, etidronate, ibandronate, risedronate) are the first-line therapy for the majority of patients and these treatments can be given either orally or intravenously. Alternative treatment options include strontium ranelate and raloxifene. Anabolic therapy with parathyroid hormone can be considered for patients with severe disease. These patients will often require referral for specialist assessment and monitoring. All patients at risk of developing osteoporosis should be given lifestyle advice regarding dietary intake of calcium and vitamin D and regular weight-bearing exercise.     

Incidence and risk factors of fractures in patients with rheumatoid arthritis: an Asian prospective cohort study

Rheumatoid arthritis (RA) patients have high risk for osteoporosis and fracture. We aimed to identify the incidence rate and risk factors of fractures in Asian RA patients. A total of 3557 RA patients in the KORean Observational study Network for Arthritis (KORONA) were included and observed over a mean follow-up of 18 months. A fracture was assessed as total, major, or minor fractures; major fracture was defined as a vertebral or hip fracture, and the other fractures were classified as minor fractures. The standardized incidence ratio (SIR) of fracture in RA patients was calculated compared with general population, and possible risk factors for fractures were explored using multivariable logistic regression analyses. A total of 194 patients with 215 fractures were observed, and the SIR of the total fracture in RA patients was 2.2 [95 % confidence interval (CI) 1.9–2.6]. The SIRs of major and minor fractures were 1.5 (CI 1.1–2.0) and 3.0 (CI 2.5–3.7), respectively. Advanced age [odds ratio (OR) 1.03, CI 1.02–1.05, p < 0.01] and having history of prior fracture (OR 2.17, CI 1.54–3.08, p < 0.01) were risk factors for total fractures. In addition, higher HAQ increased fracture risk (OR 2.02, CI 1.05–3.89, p = 0.04), whereas the use of bisphosphonate showed protective effect for future fractures (OR 0.34, CI 0.14–0.87, p = 0.02) in patients with osteoporosis. RA patients had a 2.2-fold increased risk of fractures as compared with general population. In Asian RA patients, advanced age and history of prior fracture were the most important risk factors for new fractures.     

Osteoporosis in patients with primary biliary cirrhosis

Metabolic bone disease has been recognized as an important complication of chronic liver disease particularly in cholestatic disorders [primary biliary cirrhosis (PBC) and primary sclerosing cholangitis] and after liver transplantation. It includes osteoporosis and more rarely osteomalacia, which is more frequent in severe malabsorption and advanced liver disease. The pathogenesis of this disorder is complex and is likely to be multifactorial. Regardless of the etiology of osteoporosis in PBC patients, they have an increased risk of spontaneous or low-trauma fracturing leading to significant patient morbidity, deterioration of quality of life, and even patient mortality. The development of bone densitometry has allowed assessment of bone mass and then contributed in estimating the fracture risk. The gold standard of bone mineral density measurement is currently the dual- energy X-ray absorptiometry. Recommendations formulated by the World Health Organization have reported the diagnostic ranges of osteoporosis based on the t-score: patient with osteoporosis has a t-score less than -2.5 SD, osteopenia has a t-score between -1.0 and -2.5 SD and a normal individual has a t-score more than -1.0 SD. The risk of fracture shows a correlation with bone mineral density but no fracture threshold was determined and the best site of characterizing the hip fracture risk is the measure of the bone mineral density of the proximal femur. The treatment of osteoporosis in patients with PBC is largely based on trials of patients with postmenopausal osteoporosis as there are a few and smaller studies of osteoporotic patients with PBC. Bisphosphonates seem to be effective in biliary disease and are more tolerated.     

Empfehlungen der Projektgruppe Pr?vention der DGK zur risikoadjustierten Pr?vention von Herz- und Kreislauferkrankungen

Primary prevention of coronary artery disease (CAD) is becoming increasingly important because of the treatment costs of CAD. The assessment of overall cardiovascular risk is of importance to evaluate the effectiveness of medical therapy. Risk stratification in Germany is usually performed using the PROCAM algorithm or the ESC score. If the 10-year risk of myocardial infarction (PROCAM) or cardiovascular death (ESC SCORE) exceeds 20 or 5%, respectively, intensive risk intervention including medical therapy is cost-effective and the number needed to treat (NNT) is usually?<?200. An NNT of?<?200 can also be achieved by treating a single pronounced risk factor. The CARRISMA system uses lifestyle factors in addition to conventional factors to improve risk stratification and also supports lifestyle modification. During the last two decades average life expectancy has increased by 6?years and possibilities for prevention have improved. Risk stratification for prevention should therefore be offered up to the age of 70. Risk scores support evidence-based and cost-effective prevention.     

Two years adherence to anti-osteoporotic medications in postmenopausal Israeli women

Treatment of postmenopausal osteoporosis comprises a major public health challenge requiring adherence to long-term therapy in order to prevent fractures and disability. The aim of this work was to assess long-term adherence to anti-osteoporosis treatments in Israeli postmenopausal women. We assessed 178 consecutive Metabolic Bone Diseases Unit patients, aged 67.4 ± 8.5, treated with alendronate or raloxifene. Adherence was assessed at a clinic visit after 6 months and by telephone survey 2 years after starting the therapy. After 6 months 137 (77%) patients were adhered to the treatment; 41(23%) discontinued it. Two years after initiating the therapy 78 (43.8%) continued the treatment, 39 (21.9%) discontinued it, 17 (9.6%) changed the initial drug to another anti-osteoporosis therapy, 21 (11.8%) lost to follow-up. Of 41 patients reported treatment discontinuation at 6 months 17 (41.5%) restarted the treatment with one of the anti-resorbing medications. Age, family history of osteoporosis and previous fracture history have not influenced patients’ adherence. Conclusion: Two years after the initiation of fracture prevention treatment, it was discontinued by one fifth of the patients. Neither age nor disease-related factors such as family history of osteoporosis, previous fracture history or the degree of bone loss influenced patients’ decision to adhere to treatment.     

Antiresorptive Therapy for the Prevention of Postmenopausal Osteoporosis

Osteoporosis is a condition associated with decreased bone strength and an increased fracture risk. It may be defined based on bone mineral density (BMD) with a T-score at the hip or spine of less than -2.5 standard deviations in young healthy individuals or from an osteoporotic fracture (i.e. a fracture occurring after low-energy trauma or no apparent trauma). Risk factors predisposing to fractures include: increasing age; female gender; low BMD; a prior fragility fracture; a family history of fragility fractures; low bodyweight; lack of estrogen in women (i.e. post menopause); corticosteroid use; smoking; a number of diseases; deficiency in calcium and vitamin D; an increased risk of falls (i.e. impaired vision); immobilization; and Caucasian race. The more risk factors that are present the higher the risk of fractures over the following 10 years. The need to initiate preventive therapy with anti-osteoporotic treatment increases steeply with the absolute fracture risk. Indications for referral for dual energy x-ray absorptiometry measurement of BMD include: age >65 years; age <65 years in postmenopausal women with any of the risk factors already mentioned; premature menopause (<45 years); prolonged amenorrhea (>1 year) in younger women; fragility fractures; and diseases or conditions known to lead to osteoporosis.Anti-resorptive therapies include calcium plus vitamin D, bisphosphonates (alendronate, etidronate, risedronate, ibandronate), selective estrogen receptor modulators (raloxifene), hormone replacement therapy, and calcitonin. Guidelines from several countries on when to initiate anti-resorptive therapy state that therapy may be started in patients with a prior fragility fracture (some guidelines state that in this situation no BMD measurements are necessary) or in patients with a T-score of less than -2.5 (some guidelines state that additional risk factors need to be present in this situation). Some guidelines state that anti-resorptive therapy may be initiated in patients with a T-score in the osteopenic range (from -1 to -2.5, i.e. not frank osteoporosis) in the presence of other risk factors. The cost effectiveness of anti-resorptive therapy increases with the absolute fracture risk. In some scenarios, treatment with bisphosphonates may be cost effective in a 50-year-old woman with an absolute hip fracture risk of >or=1.1% over the next 10 years.     

Assessment of the Relationship Between Age and the Effect of Risedronate Treatment in Women with Postmenopausal Osteoporosis: A Pooled Analysis of Four Studies

OBJECTIVES: To quantify the effect of age on the incidence of osteoporosis‐related fractures and of risedronate treatment on fracture risk in different age groups in women with postmenopausal osteoporosis. DESIGN: Data from four randomized, double‐blind, placebo‐controlled, Phase III studies were pooled and analyzed. PARTICIPANTS: The analysis population (N=3,229) consisted of postmenopausal women with osteoporosis as determined on the basis of prevalent vertebral fractures, low bone mineral density (BMD), or both. INTERVENTION: Patients had received risedronate 5 mg daily or placebo for 1 to 3 years. MEASUREMENTS: The endpoints of interest were the incidence of osteoporosis‐related fractures, clinical fractures, nonvertebral fractures, and morphometric vertebral fractures. The effect of age on fracture risk and treatment benefit was examined using Cox regression models with age and treatment as explanatory variables. The 3‐year fracture risk was estimated for patients in each treatment group at a given age. RESULTS: Irrespective of treatment, fracture risks were greater in older patients (P<.001). On average, for every 1‐year increase in age, a patient's risk for osteoporosis‐related fracture increased 3.6% (95% confidence interval=2.3–5.0%). Irrespective of age, risedronate treatment reduced fracture risk 42%. Risedronate‐treated patients had fracture risks similar to those of placebo‐treated patients 10 to 20 years younger. CONCLUSION: Patients treated with risedronate have a significantly lower fracture risk, similar to that of untreated patients 10 to 20 years younger.     

Absolute risk reduction in osteoporosis: assessing treatment efficacy by number needed to treat

Postmenopausal osteoporosis is a chronic condition due to decreased bone mass, leading to reduced bone strength and increased fracture risk. Currently available pharmacological treatments include antiresorptive agents (bisphosphonates and raloxifene) and bone-forming agents (strontium ranelate and two different parathyroid peptides). Comparison via reduction in relative risk of fracture may produce artificially high reductions in fracture risk for some agents. Responder analysis based on absolute risk reduction (ARR, the arithmetic difference between events rates with and without treatment over a fixed time) and a related parameter, number needed to treat (NNT, the number of patients needed to treat over a fixed time to prevent one event) may provide more reliable parameters. We reviewed placebo-controlled, randomized, double-blind, pivotal phase 3 trials employed as part of the regulatory process, in order to calculate ARRs and NNTs for vertebral and hip fracture over 3 years for antiosteoporotic agents currently available in Europe. The NNT values to prevent one vertebral fracture over 3 years range from 9 for the strontium ranelate to 21 for ibandronate. NNT values for hip fracture over 3 years range from 48 for strontium ranelate to 91 for three of the bisphosphonates. Our analysis indicates that the bone-forming agent strontium ranelate may have the lowest NNT for the prevention of both vertebral and hip fracture. Responder analysis may enable translation of clinical trial results into guidance for routine clinical practice by indicating the amount of effort needed to prevent the same event in comparable populations with different treatment options.     

Mapping translational research into individualized prognosis of fracture risk

The assessment of fracture risk has until now been based on the measurement of bone mineral density (BMD) and/or a prior fracture. Individuals with BMD T‐scores < –2.5 (e.g. osteoporosis) or with prior fractures are indicated for treatment. However, recent data have suggested that 55% of women and 74% of men who sustained a fracture did not have osteoporosis. Therefore, the current strategy reduces a small number of fractures in the general population, and new thinking is required for that majority of individuals whose BMD measurements are at or near (both sides) the current threshold of osteoporosis. An individual's absolute risk of fracture can be estimated from the individual risk profile, which includes age, BMD, weight or body mass index, prior fracture, comorbidities, corticosteroid use, lifestyle factors, and falls. Therefore, risk assessment must simultaneously consider all risk factors to which the individual is exposed. A number of prognostic models and predictive nomograms have been developed to estimate an individual's absolute risk of fracture, but they have not been externally validated. Nevertheless, these prognostic models can be effective tools for individualizing short‐term and long‐term risks of fracture, which can help patient counseling and selecting appropriate patients for intervention to maximize the benefit of fracture reduction in the general population.     

Prevalence of and risk factors for low bone mineral density in Japanese female patients with systemic lupus erythematosus

To examine the prevalence of and risk factors for low bone mineral density (BMD) (osteoporosis or osteopenia) in Japanese female patients with systemic lupus erythematosus (SLE). We performed BMD measurements by dual X-ray absorptiometry at the lumbar spine and the hip and collected basic and lifestyle-related, clinical and treatment characteristics among 58 SLE patients. Odds ratios (ORs) and their 95% confidence intervals (CIs) were assessed for associations between low BMD and selected factors among SLE patients. The mean BMD?±?SD was 0.90?±?0.17?g/cm² at the lumbar spine and 0.76?±?0.17?g/cm² at the hip. The prevalence of osteopenia (2.5 SD?<?T score?<?1 SD) was 50.0% and that of osteoporosis (T score?<?2.5 SD) was 13.8% in our SLE patients. After adjustment for age and disease duration, we found the number of deliveries (OR?=?5.58, 95% CI?=?1.31?C26.06; P?=?0.02) to be a risk factor for overall low BMD (T score?<?1 SD) and a maximal dosage of >50?mg/day of oral corticosteroids (OR?=?0.25, 95% CI?=?0.07?C0.91; P?=?0.035) as a preventive factor for low BMD at the lumbar spine. Reduced BMD, especially in spinal trabecular bone, was pronounced in Japanese female patients with SLE, particular in those with a history of delivery. A history of high-dose oral corticosteroids was associated with the preservation of BMD at the lumbar spine, however, further study is needed considering the limited sample size.     

Alteraciones del metabolismo óseo en 100 pacientes con enfermedad inflamatoria intestinal

Objectives

To evaluate the prevalence of osteopenia and osteoporosis in patients with inflammatory bowel disease (IBD) and to study the factors involved in their pathogenesis.

Methods

One hundred consecutive patients with IBD (57 women, mean age 41 years) were included in this study. Data were collected about their life habits, disease characteristics of medication use (mainly corticosteroids). Bone turnover markers were analyzed and the presence of osteoporosis or osteopenia was assessed with total hip and lumbar spine bone densitometry (DXA).

Results

Osteopenia percentages ranged from 37% (t-score measured by lumbar spine DXA) to 39% (hip DXA t-score). The prevalence of osteoporosis ranged from 2% (t-score measured by hip DXA) to 15% (lumbar spine DXA t-score). In the multivariate analysis, diagnosis of Crohn's disease (vs. ulcerative colitis; odds ratio 2.9, 95% CI 1-8.7) and the number of flares controlled by the cumulative dose of steroids (number of flares ≥3: odds ratio 8.7; 95%CI 1.6-45) were associated with a higher risk of osteopenia/osteoporosis. None of the analytical parameters significantly correlated with bone mineral density values.

Conclusions

The prevalence of osteopenia/osteoporosis is higher in patients with IBD (mainly those with Crohn's disease) than in the general population. Changes in bone metabolism seem to be more closely related to the inflammatory activity of IBD than to the steroid dose per se. Bone turnover markers did not correlate with the presence of osteopenia and osteoporosis.     

Fractures and bone mineral density in adult women with 21-hydroxylase deficiency

CONTEXT: Patients with classical congenital adrenal hyperplasia (CAH) receive lifelong, often supraphysiological, glucocorticoid therapy. Pharmacological doses of glucocorticoids are an established risk factor for osteoporosis. OBJECTIVE: Our objective was to evaluate bone mineral density (BMD), fracture prevalence, and markers of bone metabolism in adult females with CAH. DESIGN: This was a cross-sectional observational study. SETTING: Tertiary care referral centers were used in this study. PARTICIPANTS: We studied 61 women, aged 18-63 yr, with genetically verified CAH due to 21-hydroxylase deficiency. They were patients with salt wasting (n = 27), simple virilizing (n = 28), and nonclassical 21-hydroxylase deficiency (n = 6). A total of 61 age-matched women were controls. MAIN OUTCOME MEASURES: History of fractures was recorded. Total body, lumbar spine, and femoral neck BMD were measured by dual-energy x-ray absorptiometry. The World Health Organization criteria for osteopenia and osteoporosis were used. Serum marker of bone resorption, beta-C telopeptide was studied. RESULTS: The mean glucocorticoid dose in hydrocortisone equivalents was 16.9 +/- 0.9 mg/m2. Patients had lower BMD than controls at all measured sites (P < 0.001). In patients younger than 30 yr old, 48% were osteopenic vs. 12% in controls (P < 0.009). In patients 30 yr or older, 73% were osteopenic or osteoporotic vs. 21% in controls (P < 0.001). BMD was similar in the two classical forms and had no obvious relationship to genotypes. beta-C-telopeptide was decreased in older patients. More fractures were reported in patients than controls (P < 0.001). The number of vertebrae and wrist fractures almost reached significance (P = 0.058). CONCLUSIONS: Women with CAH have low BMD and increased fracture risk. BMD should be monitored, adequate prophylaxis and treatment instituted, and glucocorticoid doses optimized from puberty.     

The association between 10-year fracture risk by FRAX and osteoporotic fractures with disease activity in patients with rheumatoid arthritis

As rheumatoid arthritis (RA) is an independent risk factor for osteoporotic fractures, the severity of disease activity may correlate with fracture risk. Our objectives were to determine the prevalence of major osteoporotic and hip fractures in patients with RA and to identify the factors related to their 10-year probabilities. This study enrolled 232 patients with RA, aged 40–90 years, who participated in the Siriraj RA Cohort in 2016 and 2017. Demographic data, disease activity scores 28 (DAS28), and health assessment questionnaires (HAQ) were collected. All participants were evaluated for asymptomatic vertebral fractures by thoracolumbar spine radiography. The osteoporotic fracture risks were determined using the fracture risk assessment tool (FRAX). Most subjects were postmenopausal women in their sixth decade; the median disease duration was 12.95 years. Forty-six percent of patients had osteoporotic fractures, and most (87%) were vertebral fractures. Eighty-one patients had asymptomatic vertebral compression fractures. Of those, 57%, 25%, and 18% had low, moderate, and high 10-year probabilities of major osteoporotic fractures, respectively, while 51%, 34%, and 15% had low, moderate, and high 10-year probabilities of hip fractures, respectively. Factors significantly associated with the 10-year probabilities of major osteoporotic and hip fractures were disease duration (p 0.017, 0.009), menopause duration (p?<?0.001 both), cumulative disease activity (DAS28; p 0.004, 0.029), and cumulative functional disability (HAQ; p?<?0.001 both). Moderate to high 10-year probabilities of major osteoporotic and hip fractures are common in RA. Cumulative disease severity is a high risk for osteoporotic fractures.     

Male osteoporosis-what are the causes,diagnostic challenges,and management

Osteoporosis is underrecognized and undertreated in men, even though up to 25% of fractures in patients over the age of 50 years occur in men. Men develop osteoporosis with normal aging and accumulation of comorbidities that cause bone loss. Secondary causes of bone loss may be found in up to 60% of men with osteoporosis. Mortality in men who experience major fragility fracture is greater than in women. Diagnosis of osteoporosis in men is similar to women, based on low-trauma or fragility fractures, and/or bone mineral density dual-energy X-ray absorptiometry (DXA) T-scores at or below ?2.5. Because most clinical trials with osteoporosis drugs in men were based on bone density endpoints, not fracture reduction, the antifracture efficacy of approved treatments in men is not as well documented as that in women. Men at a high risk of fracture should be offered treatment to reduce future fractures.     

Risk factors associated with bone loss and occurrence of fragility fractures in rheumatoid arthritis patients

Aim of the work

To investigate the bone mineral density (BMD) in rheumatoid arthritis (RA) Tunisian patients, to identify the risk factors associated with its decrease and to assess the fracture risk.

Treating osteoporosis to prevent fractures: current concepts and future developments

Antiresorptive drugs, such as the bisphosphonates and the RANKL inhibitor denosumab, are currently the most widely used osteoporosis medications. These drugs increase bone mineral density (BMD) and reduce the risk of vertebral (by 40–70%), nonvertebral (by 25–40%) and hip fractures (by 40–53%) in postmenopausal women with osteoporosis. Due to the risk of rare side‐effects, the use of bisphosphonates has been limited to up to 10 years with oral bisphosphonates and 6 years with intravenous zoledronic acid. Despite their well‐proven efficacy and safety, few women at high risk of fracture are started on treatment. Case finding strategies, such as fracture risk‐based screening in primary care using the fracture risk assessment tool (FRAX) and Fracture Liaison Services, have proved effective in increasing treatment rates and reducing fracture rates. Recently, anabolic therapy with teriparatide was demonstrated to be superior to the bisphosphonate risedronate in preventing vertebral and clinical fractures in postmenopausal women with vertebral fracture. Treatment with the sclerostin antibody romosozumab increases BMD more profoundly and rapidly than alendronate and is also superior to alendronate in reducing the risk of vertebral and nonvertebral fracture in postmenopausal women with osteoporosis. For patients with severe osteoporosis and high fracture risk, bisphosphonates alone are unlikely to be able to provide long‐term protection against fracture and restore BMD. For those patients, sequential treatment, starting with a bone‐building drug (e.g. teriparatide), followed by an antiresorptive, will likely provide better long‐term fracture prevention and should be the golden standard of future osteoporosis treatment.