Incidence Of Fractures In Postmenopausal Women Research Articles

Height Loss Is an Independent Predictor of Fracture Incidence in Postmenopausal Women: The Results from the Gliwice Osteoporosis Study (GO Study).

The aim of a longitudinal, retrospective study was to establish variables predicting fracture incidence over a decade. The study sample comprises a group of 457 postmenopausal women aged over 55 years, recruited from the database of an outpatient osteoporotic clinic. Several variables with potential influence on bone status, including the measurement of body height and hip bone densitometry, were collected. BMD at the femoral neck (FN BMD) was established using a Prodigy device (Lunar, GE, USA). Current body height was compared with the maximal historical body height in early adulthood, as reported by the patient. Three hundred and ninety-four women did not have fractures during the follow up, and 63 subjects presented fractures. Subjects with fracture had lower FN BMD with a T-score of -1.86 ± 1.04 compared to -1.44 ± 0.89 in those without fractures (p < 0.001). Mean height loss (HL) was 3.47 ± 2.11 cm in fractured subjects and 2.50 ± 2.47 cm in unfractured ones, and differed significantly, p < 0.01. Fracture incidence was significantly related to age, rheumatoid arthritis, falls, and previous fractures. In the multivariable analysis using logistic regression, FN BMD, baseline fracture, and HL were identified as the significant predictors of fractures of follow up. Osteoporotic fractures in postmenopausal women were predicted by FN BMD, prior fracture(s), and HL easily established during physical examination.

Real-world treatment and fracture incidence in postmenopausal women with severe osteoporosis at high risk of fracture: a retrospective claims data analysis.

Background: Osteoporosis (OP) and its associated fractures have a significant impact on patients’ quality of life and are impacting their morbidity and mortality. For OP patients at high risk of fracture, guidelines recommend a pharmacological OP treatment. The aim of this study was to describe the real-world medication treatment of postmenopausal women with severe OP at high risk of fracture, their risk to experience a new fracture after having at least one previous fracture, and to assess the associated healthcare resource use (HCRU).Methods: This retrospective cohort study was based on anonymized German claims data (AOK PLUS). All included OP patients were female, ≥55 years old, and had a vertebral and/or femoral fracture. We conducted a cross-sectional analysis in 2018 and a longitudinal analysis, starting with an incident vertebral/femoral fracture (after or simultaneously with the first observed OP diagnosis). In both analyses, patient characteristics, rate of new incident fractures, OP treatment patterns, and HCRU associated with the treatment of patients were investigated.Results: In the cross-sectional setting, 12,180 patients with a mean age of 83.59 years were observed. Of these patients, 14.30% sustained at least one new incident fracture and 34.54% received a pharmaceutical OP treatment during 2018. In this year, 58.50% of the patients had at least one OP-related outpatient visit, and 26.35% had a fracture-related visit. In 160 patients (1.31%), at least one OP-related hospitalization was documented, and in 1,293 patients (10.62%) a fracture-related hospitalization in 2018.In the longitudinal setting, 10,323 patients with a mean age of 83.22 years were included. Of these, 18.96% experienced at least one new incident fracture within the first 12 months after the index fracture, and in total 30.85% in the entire follow-up period (mean 2.03 years). During the 12-month baseline period, 22.12% of the patients received an OP treatment. Three months after the index fracture, the proportion of treated patients remained at 22.30%. During the total follow-up time, 35.54% were prescribed with an OP treatment.Conclusion: We observed a considerable proportion of untreated patients and a high rate of subsequent fractures. The awareness for a proper risk assessment and the appropriate use of available treatments should be increased.

Abstract #983057: Effect of Abaloparatide on Bone Mineral Density and Fracture Incidence in Postmenopausal Women with Osteoporosis and Obesity

Abstract #983057: Effect of Abaloparatide on Bone Mineral Density and Fracture Incidence in Postmenopausal Women with Osteoporosis and Obesity

Fluoride in Drinking Water, Diet, and Urine in Relation to Bone Mineral Density and Fracture Incidence in Postmenopausal Women.

Background:Although randomized controlled trials (RCTs) have demonstrated that high fluoride increases bone mineral density (BMD) and skeletal fragility, observational studies of low-dose chronic exposure through drinking water (, the maximum recommended by the World Health Organization) have been inconclusive.Objective:We assessed associations of fluoride in urine, and intake via diet and drinking water, with BMD and fracture incidence in postmenopausal women exposed to drinking water fluoride .Methods:Data were from participants in the Swedish Mammography Cohort–Clinical, a population-based prospective cohort study. At baseline (2004–2009), fluoride exposure was assessed based on urine concentrations () and estimated dietary intake (including drinking water) (), and BMD was measured using dual energy X-ray absorptiometry. Incident fractures were ascertained via register-linkage through 2017. Residential history was collected to identify women with long-term consistent drinking water exposures prior to baseline.Results:At baseline, mean urine fluoride was creatinine () and mean dietary intake was (), respectively. During follow-up, 850, 529, and 187 cases of any fractures, osteoporotic fractures, and hip fractures, respectively, were ascertained. Baseline BMD was slightly higher among women in the highest vs. lowest tertiles of exposure. Fluoride exposures were positively associated with incident hip fractures, with multivariable-adjusted hazard ratios of 1.50 (95% CI: 1.04, 2.17) and 1.59 (95% CI: 1.10, 2.30), for the highest vs. lowest tertiles of urine fluoride and dietary fluoride, respectively. Associations with other fractures were less pronounced for urine fluoride, and null for dietary fluoride. Restricting the analyses to women with consistent long-term drinking water exposures prior to baseline strengthened associations between fractures and urinary fluoride.Discussion:In this cohort of postmenopausal women, the risk of fractures was increased in association with two separate indicators of fluoride exposure. Our findings are consistent with RCTs and suggest that high consumption of drinking water with a fluoride concentration of may increase both BMD and skeletal fragility in older women. https://doi.org/10.1289/EHP7404

Relationship between dietary inflammatory index and fracture incidence in postmenopausal women

İnflamasyon, inflamatuar uyaran veya doku hasarına karşı vücudun immün yanıtıdır. Akut inflamasyon yaralanma ve enfeksiyoz ajanlara karşı gelişirken, kronik inflamasyon insülin direnci, diyabet, ateroskleroz, obezite ve metabolik sendrom ile ilişkilidir. Diyet içeriği serumda CRP, IL-6 ve TNF-α gibi inflamasyon parametreleri üzerine etkisiyle kronik inflamasyona sebep olabilmektedir. Diyette gereksinimden fazla enerji alımı inflamatuar süreçleri tetikler. Bunun yanı sıra diyette yer alan makro- ve mikro besin ögeleri inflamatuar süreçler üzerinde etkilidir. Makro besin ögeleri olan karbonhidrat, protein ve yağların kaynağı, türü ve miktarı inflamasyon parametrelerini etkiler. Diyetin basit karbonhidrattan zengin olması, yüksek glisemik indeks, yüksek yağ (özellikle trans yağ asitlerinin fazlalığı) ve kolesterol içermesi CRP, TNF-α, IL-6, IL-1β gibi pro-inflamatuar moleküllerin salınımını arttırmaktadır. Buna karşın diyetin posa, MUFA ve Omega-3 içeriğinin yüksek olması ise inflamatuar yanıt oluşumuna karşı koruyucu etki göstermektedir. Mikro besin ögelerinden A, C, D ve E vitamini ile Çinko anti-inflamatuar etkiye sahiptir. İnflamatuar hücre kültürlerine retinoik asit eklendiğinde, TNF-α, IL-1β, IL-6 ve IL-12 salınımında azalma meydana gelmektedir. Uzun süre C vitamini desteği, CRP düzeyini azaltabilmektedir. D vitamini, inflamatuar sitokinlerin etkisini ve üretimini inhibe edebilmektedir. Alfa-tokoferol, IL-1β, CRP ve TNF-α düzeyini azaltabilmektedir. Çinko, sitokin üretimini regüle ederek inflamasyonu baskılayabilmektedir. Besin tüketimi genel olarak büyük bir çeşitlilik göstermektedir dolayısıyla diyetin inflamasyona etkisi incelenirken bir bütün olarak değerlendirilmelidir. Diyetin inflamatuar potansiyelini değerlendirmek amacıyla, 1950'den 2010'a kadar yayınlanan bilimsel literatüre dayanan bir algoritma ile Diyet İnflamatuar İndeksi (DII) oluşturulmuştur. Yüksek DII skorları ve inflamasyon, pro-inflamatuar sitokinlerin osteoklast aktivitesini arttırıcı osteoblast aktivitesini azaltıcı etkileri ile, özellikle kadınlarda kemik kütle yoğunluğunun azalmasına ve kırık insidansının artmasına neden olabilmektedir. Kadınlar, postmenopozal dönemde, östrojen seviyelerindeki azalma sebebiyle daha yüksek kırık riski ile karşı karşıya kalırlar. Östrojen, osteoklast apoptozunu düzenler ve pro-inflamatuar sitokinleri inhibe eder. Epidemiyolojik çalışmalardan elde edilen veriler, Postmenopozal kadınlarda sağlıklı bir beslenme düzeni ve düşük DII skorlarının kemik sağlığının korunmasında etkili ve gerekli olduğunu desteklemektedir.

Forearm bone mineral density and fracture incidence in postmenopausal women with osteoporosis: results from the ACTIVExtend phase 3 trial

SummaryAbaloparatide increased ultradistal radius bone mineral density (BMD) in the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial. Over the subsequent 24 months in ACTIVExtend, ultradistal radius BMD gains were maintained with alendronate. Conversely, 1/3 radius BMD remained stable during ALN treatment in ACTIVExtend after decreasing during ACTIVE.IntroductionAbaloparatide (ABL) increased femoral neck, total hip, and lumbar spine bone mineral density (BMD) in postmenopausal women with osteoporosis and decreased the risk of vertebral and nonvertebral fractures in ACTIVE. Effects on fracture risk and BMD were maintained subsequently with alendronate (ALN) in ACTIVExtend. In a prespecified subanalysis of ACTIVE, ABL also increased BMD at the ultradistal radius. Our objective was to determine the efficacy of ABL followed by ALN vs placebo (PBO) followed by ALN on forearm BMD and fracture risk over 43 months in ACTIVExtend.MethodsUltradistal and 1/3 radius BMD (ACTIVE baseline to month 43) were measured (ABL/ALN, n = 213; PBO/ALN, n = 233). Wrist fracture rates were estimated for the ACTIVExtend intent-to-treat population (ABL/ALN, n = 558; PBO/ALN, n = 581) by Kaplan-Meier (KM) method.ResultsAt cumulative month 25, mean increase from ACTIVE baseline in ultradistal radius BMD was 1.1% (standard error, 0.49%) with ABL/ALN vs − 0.8% (0.43%) with PBO/ALN (P < 0.01). BMD increases with ABL were maintained with ALN through month 43 in ACTIVExtend. BMD decreases at the 1/3 radius in ACTIVE (similar with ABL and PBO) were maintained through 24 months of ALN treatment in ACTIVExtend. Wrist fractures over 43 months occurred in 15 women with ABL/ALN (KM estimate, 2.8%) and 20 with PBO/ALN (KM estimate, 3.6%) (HR = 0.77, 95% CI 0.39, 1.50; P = not significant).ConclusionUltradistal radius BMD gains following treatment with ABL in ACTIVE were maintained over 24 months of ALN treatment in ACTIVExtend. Conversely, 1/3 radius BMD remained stable during ALN treatment in ACTIVExtend after decreasing during ACTIVE.Trial registrationClinicalTrials.gov: NCT01657162 submitted July 31, 2012

OR03-1 The Effect of Abaloparatide on Bone Mineral Density and Fracture Incidence in Postmenopausal Women with Osteoporosis and Osteoarthritis

Abaloparatide (ABL) is a novel, selective activator of the PTH1 receptor signaling pathway. In the 18-month Phase 3 ACTIVE study in women with postmenopausal osteoporosis (OP) (NCT01343004), ABL significantly increased bone mineral density (BMD), and decreased the risk of new vertebral (VF), nonvertebral (NVF), and clinical fractures vs placebo (PBO), and major OP fractures vs teriparatide (TPTD) and PBO. The relationship between osteoarthritis (OA) and OP is unclear. However, increased risk of fragility fracture has been associated with OA despite those patients having higher than average BMD. The objective of this post hoc analysis was to evaluate the efficacy and safety of ABL in patients with OA enrolled in ACTIVE. In ACTIVE, 2,463 postmenopausal women with OP were randomized 1:1:1 to double-blind daily ABL 80 µg or PBO, or open-label TPTD 20 µg, SC for 18 months. Patients were identified as those with medical history of ongoing “osteoarthritis”, “spinal osteoarthritis”, “nodal osteoarthritis”, or “intervertebral disc degeneration.” New VF incidence was evaluated using the modified intent-to-treat (mITT) population, other efficacy endpoints were evaluated using the ITT population. The percent mean changes in BMD from baseline to 18 months were calculated for the total hip (TH), femoral neck (FN), and lumbar spine (LS). A total of 888 patients with ongoing OA were identified in three treatment groups; ABL (n=291), PBO (n=303), and TPTD (n=294) [overall median age: 70 years; range: 50-85 years; mean FN T-score: -2.10]. Most common sites of OA were at the spine (n=336, 38%) and knee (n=328, 37%). At baseline, 196 (22%) patients had a prevalent VF, 208 (23%) reported ≥1 prior NVF within the last 5 years, and 369 (42%) had no prior fractures. Percent experiencing any new VF were 0%, 5.1%, and 0.4% in ABL, PBO, and TPTD, respectively (ABL vs PBO, P<0.001). Kaplan-Meier estimated cumulative incidence for other fracture endpoints was similar across treatment groups. At 18 months, significant increases (P<0.0001) in BMD from baseline were observed for ABL vs PBO at the TH (mean change 3.17% vs -0.35%), FN (2.81% vs -0.36%), and LS (8.78% vs 0.86%), consistent with the overall ACTIVE population results. Most common TEAEs were hypercalciuria (11% vs 10.2%), dizziness (10.7% vs 6.6%), increased creatinine clearance (8.9% vs 10.6%), upper respiratory tract infection (8.6% vs 6.9%), and back pain (7.9% vs 11.6%) for ABL vs PBO groups, respectively. Among postmenopausal women with OP enrolled in ACTIVE, in a subpopulation with prevalent OA, ABL resulted in significant reduction in risk of new VF as well as significant improvements in BMD, vs PBO. Results suggest ABL may be useful in the treatment of women with postmenopausal OP and concurrent OA, at high risk for fracture. Funding: Radius Health, Inc.

Abstract #184 Effect of Abaloparatide Followed by Alendronate on Bone Mineral Density and Fracture Incidence in Postmenopausal Women with Osteoporosis and Type 2 Diabetes Mellitus

Abstract #184 Effect of Abaloparatide Followed by Alendronate on Bone Mineral Density and Fracture Incidence in Postmenopausal Women with Osteoporosis and Type 2 Diabetes Mellitus

Efficacy of Pharmacological Therapies for the Prevention of Fractures in Postmenopausal Women: A Network Meta-Analysis.

Osteoporosis and osteopenia are associated with increased fracture incidence in postmenopausal women. We aimed to determine the comparative effectiveness of various available pharmacological therapies. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ISI Web of Science, and Scopus for randomized controlled trials that enrolled postmenopausal women with primary osteoporosis and evaluated the risk of hip, vertebral, or nonvertebral fractures. A network meta-analysis was conducted using the multivariate random effects method. We included 107 trials (193,987 postmenopausal women; mean age, 66 years; 55% white; median follow-up, 28 months). A significant reduction in hip fractures was observed with romosozumab, alendronate, zoledronate, risedronate, denosumab, estrogen with progesterone, and calcium in combination with vitamin D. A significant reduction in nonvertebral fractures was observed with abaloparatide, romosozumab, denosumab, teriparatide, alendronate, risedronate, zoledronate, lasofoxifene, tibolone, estrogen with progesterone, and vitamin D. A significant reduction in vertebral fractures was observed with abaloparatide, teriparatide, parathyroid hormone 1-84, romosozumab, strontium ranelate, denosumab, zoledronate, risedronate, alendronate, ibandronate, raloxifene, bazedoxifene, lasofoxifene, estrogen with progesterone, tibolone, and calcitonin. Teriparatide, abaloparatide, denosumab, and romosozumab were associated with the highest relative risk reductions, whereas ibandronate and selective estrogen receptor modulators had lower efficacy. The evidence for the treatment of fractures with vitamin D and calcium remains limited despite numerous large trials. This network meta-analysis provides comparative effective estimates for the various available treatments to reduce the risk of fragility fractures in postmenopausal women.

Abstract #531 Effect of Abaloparatide on Bone Mineral Density and Fracture Incidence in Postmenopausal Women with Osteoporosis and Type 2 Diabetes Mellitus

Abstract #531 Effect of Abaloparatide on Bone Mineral Density and Fracture Incidence in Postmenopausal Women with Osteoporosis and Type 2 Diabetes Mellitus

Geography of Fracture Incidence in Postmenopausal Women with Osteoporosis Treated with Abaloparatide

Geographic heterogeneity has been observed in fracture risk and efficacy of therapeutic intervention in postmenopausal osteoporosis. The objectives of these analyses were to assess across geographic and ethnic subgroups the heterogeneity of fracture incidence and baseline risk, and consistency of effect of abaloparatide-SC vs placebo on fracture risk reduction in the 18-month, phase 3, multinational, ACTIVE randomized controlled trial. Prespecified exploratory analyses of geographic subgroups (North America, South America, Europe, Asia) and post hoc analyses of ethnic subgroups (Hispanic or Latino, other) of postmenopausal women with osteoporosis enrolled in the abaloparatide-SC and placebo cohorts (n = 1645) were performed. Country-specific FRAX models were used to calculate 10-year absolute fracture risks. Relative risk reductions for vertebral fractures and hazard ratios for non-vertebral, clinical, and major osteoporotic fractures were calculated. Forest plots were constructed to assess treatment-by-subgroup interactions for each geographic region and ethnicity. Baseline prevalence of vertebral fractures was similar across geographies; baseline prevalence of non-vertebral fractures was more variable. Ten-year major osteoporosis fracture and hip fracture risks were variable across and within regions. The effects of abaloparatide-SC on reducing the risk of vertebral, non-vertebral, clinical, and major osteoporotic fractures were similar across regions, and for Hispanic or Latino vs other ethnicities. A limitation was the limited power to detect interactions with few events. In conclusion, despite geographic variability in fracture incidence and risk at baseline, no differences were detected in the effects of abaloparatide-SC in reducing vertebral, non-vertebral, clinical, and major osteoporotic fracture risk across assessed geographic regions and ethnicities.

Vitamin K₂ therapy for postmenopausal osteoporosis.

Vitamin K may play an important role in the prevention of fractures in postmenopausal women with osteoporosis. Menatetrenone is the brand name of a synthetic vitamin K2 that is chemically identical to menaquinone-4. The present review study aimed to clarify the effect of menatetrenone on the skeleton in postmenopausal women with osteoporosis, by reviewing the results of randomized controlled trials (RCTs) in the literature. RCTs that investigated the effect of menatetrenone on bone mineral density (BMD), measured by dual-energy X-ray absorptiometry and fracture incidence in postmenopausal women with osteoporosis, were identified by a PubMed search for literature published in English. Eight studies met the criteria for RCTs. Small RCTs showed that menatetrenone monotherapy decreased serum undercarboxylated osteocalcin (ucOC) concentrations, modestly increased lumbar spine BMD, and reduced the incidence of fractures (mainly vertebral fracture), and that combined alendronate and menatetrenone therapy enhanced the decrease in serum ucOC concentrations and further increased femoral neck BMD. This review of the literature revealed positive evidence for the effects of menatetrenone monotherapy on fracture incidence in postmenopausal women with osteoporosis. Further studies are required to clarify the efficacy of menatetrenone in combination with bisphosphonates against fractures in postmenopausal women with osteoporosis.

Fracture incidence after 3 years of aromatase inhibitor therapy.

The purpose of this study was to describe the fracture incidence and bone mineral density (BMD) evolution in a large cohort of post-menopausal women with breast cancer after 3 years of aromatase inhibitor (AI) therapy. A prospective, longitudinal study in real-life setting. Each woman had an extensive medical assessment, a biological evaluation, a BMD measurement, and systematic spinal X-rays at baseline and after 3 years of AI therapy. Women with osteoporosis at baseline (T-score < -2.5 and/or non-traumatic fracture history) were treated by oral weekly bisphosphonates. Among 497 women (mean age 63.8 ± 9.6 years) included in this study, 389 had a bone evaluation both at baseline and after 3 years of AI therapy: 267 women (mean age 61.2 ± 8.6) with no osteoporosis at baseline and 122 women (mean age 67.2 ± 9.1) with osteoporosis at baseline justifying a weekly oral bisphosphonate treatment. Women without bisphosphonates had a significant decrease in spine BMD (-3.5%, P < 0.01), neck BMD (-2.0%, P < 0.01), and total hip BMD (-2.1%, P < 0.01) over the 3 years but only 15 of them (5.6%) presented an incident vertebral or non-vertebral fracture. In osteoporotic women treated with bisphosphonates, spine and hip BMD were maintained at 3 years but 12 of them (9.8%) had an incident fracture. These fractured women were significantly older (74.1 ± 9.8 versus 66.5 ± 8.8) but also presented BMD loss during treatment suggesting poor adherence to bisphosphonate treatment. This real-life study confirmed that AIs induced moderate bone loss and low fracture incidence in post-menopausal women without initial osteoporosis. In women with baseline osteoporosis and AI therapy, oral bisphosphonates maintain BMD but were associated with a persistent fracture risk, particularly in older women.

Preference for wine is associated with lower hip fracture incidence in post-menopausal women.

BackgroundPast studies of relationships between alcohol and hip fracture have generally focused on total alcohol consumed and not type of alcohol. Different types of alcohol consist of varying components which may affect risk of hip fracture differentially. This study seeks to examine the relationship between alcohol consumption, with a focus on type of alcohol consumed (e.g. beer, wine, or hard liquor) and hip fracture risk in post-menopausal women.MethodsThe longitudinal cohort consisted of U.S. post-menopausal women aged 50–79 years enrolled between 1993–1998 in the Women’s Health Initiative Clinical Trials and Observational Study (N=115,655).ResultsWomen were categorized as non-drinkers, past drinkers, infrequent drinkers and drinkers by preference of alcohol type (i.e. those who preferred wine, beer, hard liquor, or who had no strong preference). Mean alcohol consumption among current drinkers was 3.3 servings per week; this was similar among those who preferred wine, beer and liquor. After adjustment for potential confounders, alcohol preference was strongly correlated with hip fracture risk (p = 0.0167); in particular, women who preferred wine were at lower risk than non-drinkers (OR=0.78; 95% CI 0.64-0.95), past drinkers (OR=0.85; 95% CI 0.72-1.00), infrequent drinkers (OR=0.73; 95% CI 0.61-0.88), hard liquor drinkers (OR=0.87; 95% CI 0.71-1.06), beer drinkers (OR=0.72; 95% CI 0.55-0.95) and those with no strong preference (OR=0.89; 95% CI 0.89; 95% CI 0.73-1.10).ConclusionsPreference of alcohol type was associated with hip fracture; women who preferentially consumed wine had a lower risk of hip fracture compared to non-drinkers, past drinkers, and those with other alcohol preferences.

Single-nucleotide polymorphisms in the P2X7 receptor gene are associated with post-menopausal bone loss and vertebral fractures

The purinergic P2X7 receptor has a major role in the regulation of osteoblast and osteoclast activity and changes in receptor function may therefore affect bone mass in vivo. The aim of this study was to determine the association of non-synonymous single-nucleotide polymorphisms in the P2RX7 gene to bone mass and fracture incidence in post-menopausal women. A total of 1694 women (aged 45-58) participating in the Danish Osteoporosis Prevention Study were genotyped for 12 functional P2X7 receptor variants. Bone mineral density was determined at baseline and after 10 years. In addition, vertebral fracture incidence was documented at 10 years. We found that the rate of bone loss was clearly associated with the Arg307Gln amino acid substitution such that individuals heterozygous for this polymorphism had a 40% increased rate of bone loss. Furthermore, individuals carrying the Ile568Asn variant allele had increased bone loss. In contrast, the Gln460Arg polymorphism was associated with protection against bone loss. The Ala348Thr polymorphism was associated with a lower vertebral fracture incidence 10 years after menopause. Finally, we developed a risk model, which integrated P2RX7 genotypes. Using this model, we found a clear association between the low-risk (high-P2X7 function) alleles and low rate of bone loss. Conversely, high-risk (reduced P2X7 function) alleles were associated with a high rate of bone loss. In conclusion, an association was demonstrated between variants that reduce P2X7 receptor function and increased rate of bone loss. These data support that the P2X7 receptor is important in regulation of bone mass.

Treatment of postmenopausal women with osteoporosis with PTH(1–84) for 36 months: treatment extension study

Objective:To determine the safety and efficacy of full-length parathyroid hormone, PTH(1–84), treatment for up to 36 months by evaluating bone mineral density (BMD) changes, bone histomorphometric indices, and clinical fracture incidence in postmenopausal women with osteoporosis.Background:The TOP trial demonstrated increased lumbar spine BMD (6.9%) versus placebo after 18 months of PTH(1–84) treatment and reduced the incidence of new vertebral fractures (61%; p = 0.001). The therapeutic benefits of long-term treatment of postmenopausal women with PTH(1–84) are unknown.Methods:The safety and efficacy of 36 months of once-daily dosing with 100 µg PTH(1–84) in postmenopausal women with osteoporosis were assessed. Women receiving placebo during the TOP trial were eligible for PTH(1–84) in the extension study.Clinical trial registration:NCT00172120.Results:Lumbar spine BMD increased by 8.5% above baseline (p < 0.001) at 36 months of PTH(1–84) treatment, remaining stable during the last 12 months of treatment. Increases in total hip and femoral neck BMD occurred more slowly, reaching 3.2% and 3.4%, respectively above baseline at 36 months (p < 0.001). The total hip BMD showed no signs of reaching a limiting value although the femoral neck plateaued from months 24 to 36. Seven patients had vertebral fractures during the placebo phase of the TOP trial and before entering the extension study, but this rate decreased with the introduction of PTH(1–84) therapy, resulting in a single worsened vertebral fracture in the first 6 months and no further vertebral fractures from months 6 to 36. Treatment over 36 months with PTH(1–84) was well-tolerated and iliac crest biopsies showed no adverse effects on bone.Limitations:There was no placebo group for BMD comparisons. The number of patients assessed for fracture incidence was small.Conclusions:PTH(1–84) treatment for 36 months resulted in significant increases in BMD at the lumbar spine and hip, was associated with a lower incidence of vertebral fracture when compared to before therapy initiation, and was well-tolerated. The continuous increases in total hip BMD suggest that prolonged PTH(1–84) treatment may be beneficial for postmenopausal osteoporosis. Increased BMD at the femoral neck and lumbar spine also showed favourable changes but plateaued between 24 and 36 months. Long-term treatment was not associated with abnormalities in bone biopsies.

Loss of hip bone mineral density over time is associated with spine and hip fracture incidence in osteoporotic postmenopausal women

The objective of the study assess the relationship between bone mineral density (BMD) loss over time and fracture incidence in postmenopausal women. This is a posthoc analysis that includes women from the placebo group of two large randomized controlled trials having assessed the efficacy of a new anti-osteoporotic drug. BMD was assessed every 6 months during 3 years at the lumbar spine, the femoral neck and the total proximal femur. Vertebral fractures were assessed using a semiquantitative method. Hip fractures were based on written documentation. All patients received calcium and vitamin D. In the present study that included 1,775 patients (with complete data at baseline and after 3 years), the logistic regression analysis, adjusted for covariates, showed that 3-year change in lumbar BMD was not statistically associated with the new vertebral fractures after 3 years. However, femoral neck and total proximal femur BMD changes was statistically correlated with the incidence of new vertebral fractures (P < 0.001). When considering change in BMD after the first year of follow-up, a decrease in total proximal femur BMD was statistically associated with an increase in the incidence of new vertebral fractures during the last 2 years of follow-up (P = 0.048). The 3-year change in femoral neck and total proximal BMD was statistically correlated with the incidence of hip and fragility fracture after 3 years (all P < 0.001). In this elderly osteoporotic population receiving calcium and vitamin D, a decrease in hip BMD after 1 or 3 year of follow-up, is associated with an increased risk of fracture incidence. However, spine BMD changes do not influence vertebral fracture incidence.

Efficacy and safety of risedronate 150 mg once a month in the treatment of postmenopausal osteoporosis

Fragility fractures that occur as a result of osteoporosis are frequently associated with chronic pain and decreased quality of life as well as significant morbidity and mortality. Fracture reduction, however, is often less than optimal due to poor compliance with medications. Studies have demonstrated that risedronate, a heterocyclic nitrogen containing bisphosphonate can reduce vertebral, nonvertebral, and hip fracture incidence in postmenopausal women, in men, and in subsets of older patients at great risk of falls and fragility. The mechanism, efficacy, dosing options, and tolerability of risedronate are reviewed.

High-dose vitamin K supplementation reduces fracture incidence in postmenopausal women: a review of the literature

Although systematic review and meta-analysis of randomized controlled trials (RCTs) have concluded that vitamin K is effective in preventing fractures, the effect of vitamin K on the skeleton remains a matter of controversy. The objective of the present review of the literature was to evaluate the effect of vitamin K supplementation on the skeleton of postmenopausal women. PubMed was used to search the reliable literature for RCTs by using the search terms "vitamin K(1) or vitamin K(2)," "bone," and "postmenopausal women" and the following inclusion criteria: approximately 50 or more subjects per group and study period of 2 years or longer. Seven RCTs met the inclusion criteria. The results of these RCTs showed that vitamin K(1) and vitamin K(2) supplementation reduced serum undercarboxylated osteocalcin levels regardless of dose but that it had inconsistent effects on serum total osteocalcin levels and no effect on bone resorption. Despite the lack of a significant change or the occurrence of only a modest increase in bone mineral density, high-dose vitamin K(1) and vitamin K(2) supplementation improved indices of bone strength in the femoral neck and reduced the incidence of clinical fractures. The review of the reliable literature confirmed the effect of vitamin K(1) and vitamin K(2) supplementation on the skeleton of postmenopausal women mediated by mechanisms other than bone mineral density and bone turnover.

Change in the use of hormone replacement therapy and the incidence of fracture in Oslo

Fracture incidence in Oslo decreased from the 1970s to the 1990s in younger postmenopausal women, but not in older women or in men. Concurrently, hormone replacement therapy increased considerably. Using data from the Oslo Health Study, we estimated that roughly half the decline might be attributed hormone replacement therapy. Between the late 1970s and the late 1990s, the incidence of hip fracture and distal forearm fracture decreased in younger postmenopausal women in Oslo, but not in elderly women or in men. The purpose of this report is to evaluate whether the decreased incidence was coherent with trends in use of hormone replacement therapy (HRT). Data on estrogens were collected from official drug statistics, data on fractures from published studies and data on bone mineral density (BMD) from the Oslo Health Study. The sale of all estrogens increased 22 times from 1979 to 1999, and the sub-category estradiol combined with progestin increased 35 times. In the corresponding period the incidence of distal forearm fracture in women aged 50-64 years decreased by 33% and hip fracture by 39%. Based on differences in BMD between users and non-users of HRT, we estimated that up to half of this decline might be due to HRT. The reduction in fracture incidence in postmenopausal women in Oslo occurred in a period with a substantial increase in the use of HRT. Future surveillance will reveal whether the last years' decline in use of HRT will be translated into increasing fracture rates.