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GLOW is an observational, longitudinal, practice-based cohort study of osteoporosis in 60,393 women aged >55 years in 10 countries on three continents. In this Review, we present insights from the first 3 years of the study. Despite cost analyses being frequently based on spine and hip fractures, we found that nonvertebral, nonhip fractures were around five times more common and doubled the use of health-care resources compared with hip and spine fractures combined. Fractures not at the four so-called major sites in FRAX® (upper arm, forearm, hip and clinical vertebral fractures) account for >40% of all fractures. The risk of fracture is increased by various comorbidities, such as Parkinson disease, multiple sclerosis and lung and heart disease. Obesity, although thought to be protective against all fractures, substantially increased the risk of fractures in the ankle or lower leg. Simple assessment by age plus fracture history has good predictive value for all fractures, but risk profiles differ for first and subsequent fractures. Fractures diminish quality of life as much or more than diabetes mellitus, arthritis and lung disease, yet women substantially underestimate their own fracture risk. Treatment rates in patients at high risk of fracture are below those recommended but might be too frequent in women at low risk. Comorbidities and the limits of current therapeutic regimens jeopardize the efficacy of drugs; new regimens should be explored for severe cases. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To investigate the prevalence and incidence of clinical fractures in obese, postmenopausal women enrolled in the Global Longitudinal study of Osteoporosis in Women (GLOW). Methods: This was a multinational, prospective, observational, population-based study carried out by 723 physician practices at 17 sites in 10 countries. A total of 60,393 women aged ≥55 years were included. Data were collected using self-administered questionnaires that covered domains that included patient characteristics, fracture history, risk factors for fracture, and anti-osteoporosis medications. Results: Body mass index (BMI) and fracture history were available at baseline and at 1 and 2 years in 44,534 women, 23.4% of whom were obese (BMI ≥30 kg/m2). Fracture prevalence in obese women at baseline was 222 per 1000 and incidence at 2 years was 61.7 per 1000, similar to rates in nonobese women (227 and 66.0 per 1000, respectively). Fractures in obese women accounted for 23% and 22% of all previous and incident fractures, respectively. The risk of incident ankle and upper leg fractures was significantly higher in obese than in nonobese women, while the risk of wrist fracture was significantly lower. Obese women with fracture were more likely to have experienced early menopause and to report 2 or more falls in the past year. Self-reported asthma, emphysema, and type 1 diabetes were all significantly more common in obese than nonobese women with incident fracture. At 2 years, 27% of obese women with incident fracture were receiving bone protective therapy, compared with 41% of nonobese and 57% of underweight women. Conclusions: Our results demonstrate that obesity is not protective against fracture in postmenopausal women and is associated with increased risk of ankle and upper leg fractures. [Copyright &y& Elsevier]

Summary A number of agents have been shown to reduce the risk of fractures in patients with postmenopausal osteoporosis. However, the additional benefits of combination therapy as opposed to monotherapy are uncertain. We performed a MEDLINE search and reviewed the published randomized trials of agents used in combination. Combination therapy results in greater gains in bone mineral density than monotherapy and possibly greater effects on bone turnover. However, none of these studies are large enough or of sufficient duration to determine whether a greater reduction in fracture is achieved. Combination therapy has important cost implications and is likely to be associated with an increased prevalence of adverse events, reduced tolerability and a reduction in adherence. Furthermore, over-suppression of bone turnover as a result of combination antiresorptive therapy might have adverse effects on bone strength, particularly with long-term treatment. Thus, the use of combination therapy for treatment of osteoporosis cannot be recommended on the basis of currently available evidence. [ABSTRACT FROM AUTHOR]

Presents a study to test the efficacy and safety of daily treatment with risedronate to reduce the risk of vertebral and other fractures in postmenopausal women with established osteoporosis. Context; Design, setting and participants; Interventions; Main outcome measures; Results; Conclusions.

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. The first approved clinical use (1977) was for treatment of Paget's disease of bone. Other approved indications are hypercalcemia of malignancy and heterotopic ossification, with a host of off-label uses (including fibrous dysplasia, periodontal disease, multiple myeloma, neuropathic arthropathy, pulmonary microlithiasis, diabetic retinopathy, bone metastases, melorheostosis, urinary stone disease, periodontal disease, etc.). Unique among bisphosphonates, etidronate (oral therapy) results in hyperphosphatemia, increased tubular reabsorption of phosphorus and increased levels of 1,25-dihydroxyvitamin D. The dose that reduces bone resorption is close to the dose that impairs mineralization; prolonged high-dose use can result in osteomalacia and bone fractures. Intermittent cyclic etidronate for osteoporosis resulted in favorable changes in bone density and histomorphometry (no mineralization defect) as well as a decrease in vertebral fracture rates in postmenopausal women with osteoporosis. Later studies showed similar effects in men with osteoporosis and patients with glucocorticoid-induced osteoporosis. Although its use for osteoporosis has given way to newer bisphosphonates and other agents, because of its unique properties, it remains the bisphosphonate of choice for treatment of heterotopic ossification. • Etidronate, a non-nitrogen-containing bisphosphonate, was the first in this class to be used clinically • In the 1970s, 80s and early 90s, etidronate was widely use for treatment of Paget's disease and osteoporosis • Clinical use has markedly diminished, but etidronate is still used for treatment of heterotopic ossification [ABSTRACT FROM AUTHOR]

Abstract: Bisphosphonates are effective in reducing bone turnover, increasing BMD and reducing fracture risk in postmenopausal women with osteoporosis. The licensed bisphosphonates exhibit some differences in potency and speed of onset and offset of action. These differences mean that different agents may be more advantageous in different situations. Uncertainties still exist around the optimum duration of treatment and treatment holidays, how best to use bisphosphonates with anabolic treatments, and the benefits of treatment in patients who do not have a BMD T-score below −2.5. This article is part of a Special Issue entitled Bisphosphonates. [Copyright &y& Elsevier]

Objective: To examine when, where and how fractures occur in postmenopausal women. Methods: We analyzed data from the Global Longitudinal Study of Osteoporosis in Women (GLOW), including women aged ≥55 years from the United States of America, Canada, Australia and seven European countries. Women completed questionnaires including fracture data at baseline and years 1, 2 and 3. Results: Among 60,393 postmenopausal women, 4122 incident fractures were reported (86% non-hip, non-vertebral [NHNV], 8% presumably clinical vertebral and 6% hip). Hip fractures were more likely to occur in spring, with little seasonal variation for NHNV or spine fractures. Hip fractures occurred equally inside or outside the home, whereas 65% of NHNV fractures occurred outside and 61% of vertebral fractures occurred inside the home. Falls preceded 68–86% of NHNV and 68–83% of hip fractures among women aged ≤64 to ≥85 years, increasing with age. About 45% of vertebral fractures were associated with falls in all age groups except those ≥85 years, when only 24% occurred after falling. Conclusion: In this multi-national cohort, fractures occurred throughout the year, with only hip fracture having a seasonal variation, with a higher proportion in spring. Hip fractures occurred equally within and outside the home, spine fractures more often in the home, and NHNV fractures outside the home. Falls were a proximate cause of most hip and NHNV fractures. Postmenopausal women at risk for fracture need counseling about reducing potentially modifiable fracture risk factors, particularly falls both inside and outside the home and during all seasons of the year. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Many women at risk of fracture do not receive anti-osteoporosis medication (AOM), while others may be receiving unnecessary treatment. Purpose: To examine the characteristics associated with AOM use among women at low and high risks of fracture. Methods: The Global Longitudinal Study of Osteoporosis in Women (GLOW) is a prospective cohort study in which data were collected, via self-administered questionnaires, from 60,393 non-institutionalized women aged ≥55years in 10 countries between October 1, 2006 and April 30, 2008. This is a cross-sectional analysis of baseline USA data, in which women were classified as having low fracture risk (<65years; no FRAX risk factors) or high fracture risk (≥65years; prior fracture or ≥2 other FRAX risk factors). Results: Of 27,957 women, 3013 were at low risk of fracture and 3699 were at high risk. Only 35.7% of high-risk women reported AOM treatment, rising to 39.5% for those with self-reported osteopenia and 65.4% for those with self-reported osteoporosis. Conversely, 13.4% of low-risk women reported AOM, rising to 28.7% for osteopenia and 62.4% for osteoporosis. Characteristics associated with significantly higher AOM treatment rates among low- and high-risk women were: osteoporosis (odds ratios 75.3 and 18.1, respectively), osteopenia (17.9 and 6.3), concern about osteoporosis (2.0 and 1.8), higher perceived risk of fracture (2.3 and 1.6), and higher vitality score (1.7 and 1.6). Conclusion: Use of AOM is frequently inconsistent with published guidelines in both high- and low-risk women. Characteristics other than FRAX fracture risk appear to influence this use, particularly the presence of self-reported osteoporosis. [Copyright &y& Elsevier]

Background: Although many studies have assessed the effects of estrogen and raloxifene hydrochloride on bone mineral density and serum lipid concentrations, there are few direct comparative data. Methods: Randomized placebo-controlled trial for 3 years, intention-to-treat analysis. Six hundred nineteen postmenopausal women with prior hysterectomy (mean age, 53.0 years) were studied in 38 centers in Europe, North America, Australasia, and South Africa. They were randomized to 60 mg/d or 150 mg/d of raloxifene, 0.625 mg/d of conjugated equine estrogen (CEE), or placebo. Bone density of the lumbar spine and proximal femur, biochemical markers of bone turnover, and fasting serum lipid concentrations were assessed for 3 years. Results: Compared with baseline, bone density in the lumbar spine progressively declined by 2.0% in the placebo group (P<.05), was stable in the 2 raloxifene groups, and increased 4.6% in the subjects receiving CEE (P<.001). Effects in both raloxifene groups were different from those observed in the CEE and placebo groups (P<.001). Bone density in the total hip showed similar results. Conjugated equine estrogen produced significantly greater depression of serum osteocalcin, bone-specific alkaline phosphatase, and urine C-telopeptide, compared with raloxifene. Each of the active treatments caused comparable depression of low-density lipoprotein cholesterol below placebo levels (P<.001 at most time points). Raloxifene did not affect high-density lipoprotein cholesterol, whereas CEE increased it by 13.4% compared with placebo at 3 years (P<.001). Triglyceride concentrations increased 24.6% in the CEE group at 3 years (P<.003), a significantly greater change than in the raloxifene groups, which were 4.9% and 8.0% above baseline (P&les;.002) but not different from placebo. Urinary incontinence was reported in 11 women receiving CEE, but in only 1 or 2 in each of the other groups (P&les;.01 compared with the other groups). Hernias occurred less frequently in those receiving 150 mg/d of raloxifene or CEE (P=.03 vs placebo). Conclusions: Raloxifene and CEE have beneficial effects on bone density and bone turnover, although effects of CEE are more marked. Raloxifene and CEE produce different patterns of lipid responses and have distinct adverse effect profiles. [ABSTRACT FROM AUTHOR]