Comparative effects of teriparatide and ibandronate on spine bone mineral density (BMD) and microarchitecture (TBS) in postmenopausal women with osteoporosis: a 2-year open-label study

UNLABELLED Treatment effects over 2 years of teriparatide vs. ibandronate in postmenopausal women with osteoporosis were compared using lumbar spine bone mineral density (BMD) and trabecular bone score (TBS). Teriparatide induced larger increases in BMD and TBS compared to ibandronate, suggesting a more pronounced effect on bone microarchitecture of the bone anabolic drug. INTRODUCTION The trabecular bone score (TBS) is an index of bone microarchitecture, independent of bone mineral density (BMD), calculated from anteroposterior spine dual X-ray absorptiometry (DXA) scans. The potential role of TBS for monitoring treatment response with bone-active substances is not established. The aim of this study was to compare the effects of recombinant human 1-34 parathyroid hormone (teriparatide) and the bisphosphonate ibandronate (IBN), on lumbar spine (LS) BMD and TBS in postmenopausal women with osteoporosis. METHODS Two patient groups with matched age, body mass index (BMI), and baseline LS BMD, treated with either daily subcutaneous teriparatide (N = 65) or quarterly intravenous IBN (N = 122) during 2 years and with available LS BMD measurements at baseline and 2 years after treatment initiation were compared. RESULTS Baseline characteristics (overall mean ± SD) were similar between groups in terms of age 67.9 ± 7.4 years, body mass index 23.8 ± 3.8 kg/m(2), BMD L1-L4 0.741 ± 0.100 g/cm(2), and TBS 1.208 ± 0.100. Over 24 months, teriparatide induced a significantly larger increase in LS BMD and TBS than IBN (+7.6 % ± 6.3 vs. +2.9 % ± 3.3 and +4.3 % ± 6.6 vs. +0.3 % ± 4.1, respectively; P < 0.0001 for both). LS BMD and TBS were only weakly correlated at baseline (r (2) = 0.04) with no correlation between the changes in BMD and TBS over 24 months. CONCLUSIONS In postmenopausal women with osteoporosis, a 2-year treatment with teriparatide led to a significantly larger increase in LS BMD and TBS than IBN, suggesting that teriparatide had more pronounced effects on bone microarchitecture than IBN.

Bone mineral density (BMD) and vertebral trabecular bone score (TBS) for the identification of elderly women at high risk for fracture: the SEMOF cohort study

PURPOSE To determine the predictive value of the vertebral trabecular bone score (TBS) alone or in addition to bone mineral density (BMD) with regard to fracture risk. METHODS Retrospective analysis of the relative contribution of BMD [measured at the femoral neck (FN), total hip (TH), and lumbar spine (LS)] and TBS with regard to the risk of incident clinical fractures in a representative cohort of elderly post-menopausal women previously participating in the Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture Risk study. RESULTS Complete datasets were available for 556 of 701 women (79 %). Mean age 76.1 years, LS BMD 0.863 g/cm(2), and TBS 1.195. LS BMD and LS TBS were moderately correlated (r (2) = 0.25). After a mean of 2.7 ± 0.8 years of follow-up, the incidence of fragility fractures was 9.4 %. Age- and BMI-adjusted hazard ratios per standard deviation decrease (95 % confidence intervals) were 1.58 (1.16-2.16), 1.77 (1.31-2.39), and 1.59 (1.21-2.09) for LS, FN, and TH BMD, respectively, and 2.01 (1.54-2.63) for TBS. Whereas 58 and 60 % of fragility fractures occurred in women with BMD T score ≤-2.5 and a TBS <1.150, respectively, combining these two thresholds identified 77 % of all women with an osteoporotic fracture. CONCLUSIONS Lumbar spine TBS alone or in combination with BMD predicted incident clinical fracture risk in a representative population-based sample of elderly post-menopausal women.

Further reductions in nonvertebral fracture rate with long-term denosumab treatment in the FREEDOM open-label extension and influence of hip bone mineral density after 3 years

Limited data exist on the efficacy of long-term therapies for osteoporosis. In osteoporotic postmenopausal women receiving denosumab for 7 years, nonvertebral fracture rates significantly decreased in years 4-7 versus years 1-3. This is the first demonstration of a further benefit on fracture outcomes with long-term therapy for osteoporosis. INTRODUCTION This study aimed to evaluate whether denosumab treatment continued beyond 3 years is associated with a further reduction in nonvertebral fracture rates. METHODS Participants who completed the 3-year placebo-controlled Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months (FREEDOM) study were invited to participate in an open-label extension. The present analysis includes 4,074 postmenopausal women with osteoporosis (n = 2,343 long-term; n = 1,731 cross-over) who enrolled in the extension, missed ≤1 dose during their first 3 years of denosumab treatment, and continued into the fourth year of treatment. Comparison of nonvertebral fracture rates during years 1-3 of denosumab with that of the fourth year and with the rate during years 4-7 was evaluated. RESULTS For the combined group, the nonvertebral fracture rate per 100 participant-years was 2.15 for the first 3 years of denosumab treatment (referent) and 1.36 in the fourth year (rate ratio [RR] = 0.64; 95 % confidence interval (CI) = 0.48 to 0.85, p = 0.003). Comparable findings were observed in the groups separately and when nonvertebral fracture rates during years 1-3 were compared to years 4-7 in the long-term group (RR = 0.79; 95 % CI = 0.62 to 1.00, p = 0.046). Fracture rate reductions in year 4 were most prominent in subjects with persisting low hip bone mineral density (BMD). CONCLUSIONS Denosumab treatment beyond 3 years was associated with a further reduction in nonvertebral fracture rate that persisted through 7 years of continuous denosumab administration. The degree to which denosumab further reduces nonvertebral fracture risk appears influenced by the hip bone density achieved with initial therapy.

Bone mineral density and incidence of stroke: European Prospective Investigation into Caner-Norfolk population-based study, systematic review and meta-analysis : European Prospective Investigation into Cancer - Norfolk population–based study, systematic review, and meta-analysis

Peer reviewed

Body composition and bone mineral density in male adults with hyperthyroidism. Which association?

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Hearing sensitivity and bone mineral density in older adults: the Health, Aging and Body Composition Study

Bone mineral density (BMD) may be associated with hearing loss in older adults. Demineralization of the cochlear capsule has been associated with hearing loss in those with Paget's disease of the bone and otosclerosis. Osteoporosis may also result in cochlear capsule demineralization. We hypothesized that lower hip BMD and lower heel ultrasound measurements would be associated with hearing loss in a population-based sample of 2,089 older black and white men and women. Bone parameters and hearing function were measured at the fourth clinical follow-up visit. Audiometric threshold testing was used to measure air- and bone-conduction hearing sensitivity. BMD of the hip and its subregions was measured using dual-energy X-ray absorptiometry. Calcaneal bone measurements [broadband ultrasound attenuation (BUA), speed of sound (SOS) and the quantitative ultrasound index (QUI)] were obtained using heel ultrasound. After adjusting for known hearing loss risk factors, no association was found between hearing and any of the bone measurements in whites and black women. In black men, however, lower hip BMD was associated with higher odds of hearing loss; for each standard deviation decrease in total hip BMD, the odds of hearing loss were 1.41 (95% confidence interval 1.08, 1.83), 1.39 (95% CI 1.07, 1.82) for femoral neck BMD and 1.65 (95% CI 1.26, 2.16) for trochanter BMD. Conductive hearing loss was associated with lower heel ultrasound measurements, though only among white men. The results of this study are mixed and inconclusive. Lower BMD of the hip and its subregions was associated with hearing loss among black men, but not among whites or black women. Lower measurements on heel ultrasound were associated with conductive hearing loss, though only among white men. These results suggest that axial and appendicular bone parameters may be modestly associated with hearing loss in older men, but not in women.

Change in lean body mass Is a major determinant of change in areal bone mineral density of the proximal femur: A 12-year observational study

Our objective was to assess the contribution of lean body mass (LBM) and fat body mass (FBM) to areal bone mineral density (aBMD) in women during the years surrounding menopause. We used a 12-year observational design. Participants included 75 Caucasian women who were premenopausal, 53 of whom were available for follow-up. There were two measurement periods: baseline and 12-year follow-up. At both measurement periods, bone mineral content and aBMD of the proximal femur, posterior-anterior lumbar spine, and total body was assessed using dual-energy X-ray absorptiometry (DXA). LBM and FBM were derived from the total-body scans. General health, including current menopausal status, hormone replace therapy use, medication use, and physical activity, was assessed by questionnaires. At the end of the study, 44% of the women were postmenopausal. After controlling for baseline aBMD, current menopausal status, and current hormone replacement therapy, we found that change in LBM was independently associated with change in aBMD of the proximal femur (P = 0.001). The cross-sectional analyses also indicated that LBM was a significant determinant of aBMD of all three DXA-scanned sites at both baseline and follow-up. These novel longitudinal data highlight the important contribution of LBM to the maintenance of proximal femur bone mass at a key time in women's life span, the years surrounding menopause.

Vitamin E homologues α - and γ-tocopherol are not associated with bone turnover markers or bone mineral density in perimenopausal and postmenopausal women

This study was supported by the Foods Standards Agency and the UK Department of Health (grant number N05086) and the Scottish Funding Council. We are grateful for funding from the Scottish Government's Rural and Environmental Science and Analytical Services (RESAS) Food, Land and People Programme. Any views expressed are the authors’ own; none of the funders had a role in design, analysis, or writing of the present study.

In silico methods to evaluate Fracture Risk and Bone Mineral Density changes in patients undergoing Total Hip Replacement

La sostituzione totale d’anca è uno degli interventi chirurgici con le più alte percentuali di successo. Esistono due varianti di protesi d’anca che differiscono in base al metodo di ancoraggio all’osso: cementate (fissaggio tramite cemento osseo) e non cementate (fissaggio tramite forzamento). Ad oggi, i chirurghi non hanno indicazioni quantitative di supporto per la scelta fra le due tipologie di impianto, decidendo solo in base alla loro esperienza. Due delle problematiche che interessano le protesi non cementate sono la possibilità di frattura intra-operatoria durante l’inserimento forzato e il riassorbimento osseo nel periodo di tempo successivo all’intervento. A partire da rilevazioni densitometriche effettuate su immagini da TC di pazienti sottoposti a protesi d’anca non cementata, sono stati sviluppati due metodi: 1) per la valutazione del rischio di frattura intra-operatorio tramite analisi agli elementi finiti; 2) per la valutazione della variazione di densità minerale ossea (tridimensionalmente attorno alla protesi) dopo un anno dall’operazione. Un campione di 5 pazienti è stato selezionato per testare le procedure. Ciascuno dei pazienti è stato scansionato tramite TC in tre momenti differenti: una acquisita prima dell’operazione (pre-op), le altre due acquisite 24 ore (post 24h) e 1 anno dopo l’operazione (post 1y). I risultati ottenuti hanno confermato la fattibilità di entrambi i metodi, riuscendo inoltre a distinguere e a quantificare delle differenze fra i vari pazienti. La fattibilità di entrambe le metodologie suggerisce la loro possibilità di impiego in ambito clinico: 1) conoscere la stima del rischio di frattura intra-operatorio può servire come strumento di guida per il chirurgo nella scelta dell’impianto protesico ottimale; 2) conoscere la variazione di densità minerale ossea dopo un anno dall’operazione può essere utilizzato come strumento di monitoraggio post-operatorio del paziente.

Changes in bone mineral density in the year after critical illness

RATIONALE: Critical illness may be associated with increased bone turnover and loss of bone mineral density. Prospective evidence describing long-term changes in bone mineral density after critical illness is needed to further define this relationship.

OBJECTIVES: To measure the change in bone mineral density and bone turnover markers in patients one year after critical illness compared to population-based controls.

METHODS: We studied adult patients admitted to a tertiary intensive care unit (ICU) and requiring mechanical ventilation for at least 24 hours. We measured clinical characteristics, bone turnover markers and bone mineral density during admission and one year after ICU discharge. We compared change in bone mineral density to age and sex-matched controls from the Geelong Osteoporosis Study.

MEASUREMENTS AND MAIN RESULTS: Sixty-six patients completed bone mineral density testing. Bone mineral density decreased significantly in the year after critical illness at both femoral neck and anterior-posterior spine site. The annual decrease was significantly greater in the ICU cohort compared to matched controls (anterior-posterior spine -1.59%, 95% CI -2.18, -1.01, p< 0.001, femoral neck -1.20%, 95% CI -1.69, -0.70, p <0.001). There was a significant increase in 10-year fracture risk for major fractures (4.85+5.25 vs 5.50+5.52, p<0.001) and hip fractures (1.57+2.40 vs 1.79+2.69, p=0.001). The pattern of bone resorption markers was consistent with accelerated bone turnover.

CONCLUSIONS: Critically ill patients experience a significantly greater decrease in bone mineral density in the year after admission compared to population-based controls. Their bone turnover biomarkers pattern is consistent with increased rate of bone loss.