The use of denosumab in osteoporosis - an update on efficacy and drug safety.

Introduction: Denosumab (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 Covered: Denosumab has been shown to improve bone mineral density and reduce the incidence of new fractures in postmenopausal women and men.

Update on Atypical Femoral Fractures.

➤ Atypical femoral fractures (AFFs) are stress fractures between the lesser trochanter and the metaphyseal flare that are most commonly related to prolonged (3 to 5 years) antiresorptive medication use.➤ An important finding is a visible transverse line in the lateral cortex, known as the "dreaded black line." Complete fractures are transverse and have minimal comminution.

Race and Ethnicity and Fracture Prediction Among Younger Postmenopausal Women in the Women's Health Initiative Study.

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.

Long-Term Safety and Efficacy of Recombinant Human Parathyroid Hormone (1-84) in Adults With Chronic Hypoparathyroidism.

Context: Chronic hypoparathyroidism is conventionally treated with oral calcium and active vitamin D to reach and maintain targeted serum calcium and phosphorus levels, but some patients remain inadequately controlled.

Objective: To assess long-term safety and efficacy of recombinant human parathyroid hormone (1-84) (rhPTH(1-84)) treatment.

Methods: This was an open-label extension study at 12 US centers.

Linzagolix with and without hormonal add-back therapy for the treatment of symptomatic uterine fibroids: two randomised, placebo-controlled, phase 3 trials.

Background: Uterine fibroids are common non-cancerous neoplasm that cause heavy menstrual bleeding and other signs. Linzagolix is an oral gonadotropin-releasing hormone receptor antagonist taken once per day that dose-dependently suppresses gonadal steroids and might reduce uterine-fibroid-associated signs. Two phase 3 trials were conducted to confirm the efficacy and safety of linzagolix at full-suppression (200 mg) and partial-suppression (100 mg) doses with or without hormonal add-back therapy (1 mg oestradiol and 0·5 mg norethisterone acetate) compared with placebo for the treatment of symptomatic uterine fibroids.

Understanding Physicians' Perceptions of Patient-Identified Barriers to Osteoporosis Medication Initiation: A Cognitive Mapping Approach.

Objective: Interventions to initiate medication and increase adherence for postmenopausal women who have had a fragility fracture were not always successful. The purpose of this study was to derive an empirical framework for patient-identified barriers to osteoporosis medication initiation and adherence from physician experts.

Methods: A cognitive mapping approach involving nominal group technique (NGT) meetings and a card sorting and rating task were used to obtain formative data.

Bone Mineral Density Changes Associated With Pregnancy, Lactation, and Medical Treatments in Premenopausal Women and Effects Later in Life.

Bone mineral density (BMD) changes during the life span, increasing rapidly during adolescence, plateauing in the third decade of life, and subsequently entering a phase of age-related decline. In women, menopause leads to accelerated bone loss and an increase in fracture risk. Between peak bone mass attainment and menopause, BMD is generally stable and the risk of fracture is typically low.

Updates on Osteoporosis in Men.

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.

Estimating the Effect of Elagolix Treatment for Endometriosis on Postmenopausal Bone Outcomes: A Model Bridging Phase III Trials to an Older Real-World Population.

Elagolix, a gonadotrophin-releasing hormone antagonist, is used in premenopausal women with endometriosis. There is a risk of bone loss with elagolix, but the long-term effects of BMD loss later in life cannot be directly assessed and has not been quantified. To address this gap in knowledge, this study indirectly estimated the impact of elagolix on postmenopausal fracture risk.

Pharmacologic intervention for prevention of fractures in osteopenic and osteoporotic postmenopausal women: Systemic review and meta-analysis.

Objectives: Emerging evidence has indicated a role for pharmacologic agents in the primary prevention of osteoporotic fracture, but have not yet been systematically reviewed for meta-analysis. We conducted a meta-analysis to evaluate the efficacy of pharmacologic interventions in reducing fracture risk and increasing bone mineral density (BMD) in postmenopausal women with osteopenia or osteoporosis but without prevalent fragility fracture.

Method: The Medline, EMBASE, and CENTRAL databases were searched from inception to September 30, 2019.

Serial Bone Density Measurement and Incident Fracture Risk Discrimination in Postmenopausal Women.

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.

Elagolix Treatment for Up to 12 Months in Women With Heavy Menstrual Bleeding and Uterine Leiomyomas.

Objective: To investigate the safety and efficacy of elagolix, an oral gonadotropin-releasing hormone antagonist, with hormonal add-back therapy for up to 12 months in women with heavy menstrual bleeding associated with uterine leiomyomas.

Methods: Elaris UF-EXTEND was a phase 3 extension study that evaluated an additional 6 months (up to 12 months total) of elagolix 300 mg twice daily with hormonal add-back therapy (estradiol 1 mg and norethindrone acetate 0.5 mg once daily) in women who completed an initial 6 months of the same treatment in one of two preceding phase 3 studies.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS/AMERICAN COLLEGE OF ENDOCRINOLOGY CLINICAL PRACTICE GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS- 2020 UPDATE .

The development of these guidelines is sponsored by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPGs). Recommendations are based on diligent reviews of the clinical evidence with transparent incorporation of subjective factors, according to established AACE/ACE guidelines for guidelines protocols. The Executive Summary of this 2020 updated guideline contains 52 recommendations: 21 Grade A (40%), 24 Grade B (46%), 7 Grade C (14%), and no Grade D (0%).

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS/AMERICAN COLLEGE OF ENDOCRINOLOGY CLINICAL PRACTICE GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS-2020 UPDATE.

The development of these guidelines is sponsored by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPGs). Recommendations are based on diligent reviews of the clinical evidence with transparent incorporation of subjective factors, according to established AACE/ACE guidelines for guidelines protocols. The Executive Summary of this 2020 updated guideline contains 52 recommendations: 21 Grade A (40%), 24 Grade B (46%), 7 Grade C (14%), and no Grade D (0%).

Elagolix for Heavy Menstrual Bleeding in Women with Uterine Fibroids.

Background: Uterine fibroids are hormone-responsive neoplasms that are associated with heavy menstrual bleeding. Elagolix, an oral gonadotropin-releasing hormone antagonist resulting in rapid, reversible suppression of ovarian sex hormones, may reduce fibroid-associated bleeding.

Methods: We conducted two identical, double-blind, randomized, placebo-controlled, 6-month phase 3 trials (Elaris Uterine Fibroids 1 and 2 [UF-1 and UF-2]) to evaluate the efficacy and safety of elagolix at a dose of 300 mg twice daily with hormonal "add-back" therapy (to replace reduced levels of endogenous hormones; in this case, estradiol, 1 mg, and norethindrone acetate, 0.

History of etidronate.

Etidronate is a non-nitrogen-containing bisphosphonate. Because it binds with calcium and inhibits crystal formation and dissolution, it was considered by Procter & Gamble as an additive to toothpaste (to prevent build-up of tartar) and detergent (to bind calcium and increase sudsing in "hard" water). The first clinical use (1968) was for fibrodysplasia ossificans progressiva.

Do Additional Clinical Risk Factors Improve the Performance of Fracture Risk Assessment Tool (FRAX) Among Postmenopausal Women? Findings From the Women's Health Initiative Observational Study and Clinical Trials.

The ability of the fracture risk assessment tool (FRAX) to discriminate between women who do and do not experience major osteoporotic fractures (MOFs) is suboptimal. Adding common clinical risk factors may improve discrimination. We used data from the Womens Health Initiative, a prospective study of women aged 50 to 79 years at baseline ( = 99,413; = 5722 in BMD subset) enrolled at 40 US clinical centers.