Femoral and vertebral strength improvements in postmenopausal women with osteoporosis treated with denosumab

In the randomized, placebo-controlled FREEDOM study of women aged 60 to 90 years with postmenopausal osteoporosis, treatment with denosumab once every 6 months for 36 months significantly reduced hip and new vertebral fracture risk by 40% and 68%, respectively. To gain further insight into this efficacy, we performed a nonlinear finite element analysis (FEA) of hip and spine quantitative computed tomography (QCT) scans to estimate hip and spine strength in a subset of FREEDOM subjects (n=48 placebo; n=51 denosumab) at baseline, 12, 24, and 36 months. We found that, compared with baseline, the finite element estimates of hip strength increased from 12 months (5.3%; p<0.0001) and through 36 months (8.6%; p<0.0001) in the denosumab group. For the placebo group, hip strength did not change at 12 months and decreased at 36 months (-5.6%; p<0.0001). Similar changes were observed at the spine: strength increased by 18.2% at 36 months for the denosumab group (p<0.0001) and decreased by -4.2% for the placebo group (p=0.002). At 36 months, hip and spine strength increased for the denosumab group compared with the placebo group by 14.3% (p<0.0001) and 22.4% (p<0.0001), respectively. Further analysis of the finite element models indicated that strength associated with the trabecular bone was lost at the hip and spine in the placebo group, whereas strength associated with both the trabecular and cortical bone improved in the denosumab group. In conclusion, treatment with denosumab increased hip and spine strength as estimated by FEA of QCT scans compared with both baseline and placebo owing to positive treatment effects in both the trabecular and cortical bone compartments. These findings provide insight into the mechanism by which denosumab reduces fracture risk for postmenopausal women with osteoporosis

ÁREA DE PRESIDENCIA [Material gráfico]

Forma parte del reportaje fotográfico sobre la inauguración en los años 40 del nuevo edificio institucional del Cabildo de Gran CanariaCopia digital. Madrid : Ministerio de Educación, Cultura y Deporte. Subdirección General de Coordinación Bibliotecaria, 201

Romosozumab Enhances Vertebral Bone Structure in Women With Low Bone Density.

Funder: NIHR Cambridge BRC; Id: http://dx.doi.org/10.13039/501100018956Romosozumab monoclonal antibody treatment works by binding sclerostin and causing rapid stimulation of bone formation while decreasing bone resorption. The location and local magnitude of vertebral bone accrual by romosozumab and how it compares to teriparatide remains to be investigated. Here we analyzed the data from a study collecting lumbar computed tomography (CT) spine scans at enrollment and 12 months post-treatment with romosozumab (210 mg sc monthly, n = 17), open-label daily teriparatide (20 μg sc, n = 19), or placebo (sc monthly, n = 20). For each of the 56 women, cortical thickness (Ct.Th), endocortical thickness (Ec.Th), cortical bone mineral density (Ct.bone mineral density (BMD)), cancellous BMD (Cn.BMD), and cortical mass surface density (CMSD) were measured across the first lumbar vertebral surface. In addition, color maps of the changes in the lumbar vertebrae structure were statistically analyzed and then visualized on the bone surface. At 12 months, romosozumab improved all parameters significantly over placebo and resulted in a mean vertebral Ct.Th increase of 10.3% versus 4.3% for teriparatide, an Ec.Th increase of 137.6% versus 47.5% for teriparatide, a Ct.BMD increase of 2.1% versus a -0.1% decrease for teriparatide, and a CMSD increase of 12.4% versus 3.8% for teriparatide. For all these measurements, the differences between romosozumab and teriparatide were statistically significant (p < 0.05). There was no significant difference between the romosozumab-associated Cn.BMD gains of 22.2% versus 18.1% for teriparatide, but both were significantly greater compared with the change in the placebo group (-4.6%, p < 0.05). Cortical maps showed the topographical locations of the increase in bone in fracture-prone areas of the vertebral shell, walls, and endplates. This study confirms widespread vertebral bone accrual with romosozumab or teriparatide treatment and provides new insights into how the rapid prevention of vertebral fractures is achieved in women with osteoporosis using these anabolic agents. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).This research was funded by Amgen and supported by the NIHR Cambridge BRC. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care

ZOLEDRONOVAYa KISLOTA V PROFILAKTIKE POTERI KOSTNOY TKANI U zhENShchIN POSTMENOPAUZAL'NOGO VOZRASTA S OSTEOPENIEY

Профилактика остеопоротических переломов, особенно бедренной кости и позвонков, - это важная проблема здравоохранения. Подобные переломы сопровождаются повышенным риском осложнений и смерти, поэтому эффективная стратегия их профилактики может оказать значительное влияние на заболеваемость и несколько меньшее, но существенное влияние на смертность пожилых людей. 1-3 Хотя у женщин с остепенией риск развития переломов ниже, чем у женщин того же возраста с остеопорозом, тем не менее, при отсутствии лечения у них высока вероятность развития остеопороза. Более того, большинство переломов регистрируют у пациенток с остеопенией. 4 В последних рекомендациях женщинам постменопаузального возраста с остеопенией и со средним или высоким риском переломов (оценивают с помощью валидированных методов, таких как FRAX) предлагается назначать лекарственные средства, предназначенные для лечения остеопороза. 5 Пероральные бисфосфонаты предупреждают потерю костной ткани после наступления менопаузы у женщин более молодого и старшего возраста 6-8 Однако в клинической практике многие пациентки плохо выполняют рекомендации врача и принимают пероральные бисфосфонаты в течение не более нескольких месяцев. 9 В связи с этим важное значение имеет применение эффективного препарата, обеспечивающего высокую приверженность пациенток. В клинических исследованиях доказано, что ежегодные инфузии золедроновой кислоты в дозе 5 мг в течение 3 лет снижают риск переломов позвонков, бедренной кости и внепозвоночных переломов и увеличивают МПК поясничных позвонков и бедренной кости у женщин с постменопаузальным остеопорозом. 10 Кроме того, препарат снижал риск повторных клинически явных переломов у мужчин и женщин, недавно перенесших остеопоротический перелом бедренной кости. 11 Целью данного исследования было изучение эффективности и переносимости внутривенных инфузий золедроновой кислоты в дозе 5 мг у женщин постменопаузального возраста с остеопенией. В 2-летнем исследовании изучали эффективность двух и одной инфузии препарата, чтобы оценить возможность сокращения числа инфузий для профилактики потери костной ткани

Baseline Glucocorticoid Dose and Bone Mineral Density Response with Teriparatide or Alendronate Therapy in Patients with Glucocorticoid-induced Osteoporosis

Objective. This post-hoc analysis studied the effect of baseline glucocorticoid dose on the 18-month bone mineral density (BMD) response to teriparatide 20 mu g/day or alendronate 10 mg/day in 387 patients with glucocorticoid-induced osteoporosis (GIO) from a randomized, double-blind trial. Methods. Lumbar spine (LS), femoral neck (FN), and total hip (TH) BMD were measured at baseline and 18 months. Mean baseline glucocorticoid dose was categorized as low ( 5 and = 15 mg/day). Results. Baseline LS, FN, and TH BMD were similar between groups, and between glucocorticoid dose categories within each group. LS BMD increases at the low, medium, and high glucocorticoid doses were 8.1%, 6.6%, and 4.6%, respectively, with teriparatide, and 3.6%, 2.8%, and 2.3% with alendronate. Analyzed as a continuous variable, higher glucocorticoid doses had a negative, but nonsignificant, effect on the percentage increase in LS BMD in both groups. Glucocorticoid dose did not significantly affect FN or TH BMD increases in either group. Across the 3 glucocorticoid dose categories, the overall LS BMD increases were different for both treatments combined (p = 0.033), but the relative differences between the treatment groups were not different (interaction, p = 0.52). Conclusion. Teriparatide and alendronate increased LS and hip BMD across a range of baseline glucocorticoid doses. LS BMD increases with teriparatide were greater in the low-dose category than in the high-dose category. Overall LS BMD increases were significantly greater with teriparatide compared with alendronate, which may reflect the respective anabolic and antiresorptive mechanisms of action. Clinical Trial Registry Number: NCT00051558. (First Release Nov 15 2009; J Rheumatol 2010;37:141-8; doi:10.3899/jrheum.090411

Baseline Glucocorticoid Dose and Bone Mineral Density Response with Teriparatide or Alendronate Therapy in Patients with Glucocorticoid-induced Osteoporosis

ABSTRACT. Objective. This post-hoc analysis studied the effect of baseline glucocorticoid dose on the 18-month bone mineral density (BMD) response to teriparatide 20 µg/day or alendronate 10 mg/day in 387 patients with glucocorticoid-induced osteoporosis (GIO) from a randomized, double-blind trial. Methods. Lumbar spine (LS), femoral neck (FN), and total hip (TH) BMD were measured at baseline and 18 months. Mean baseline glucocorticoid dose was categorized as low (≤ 5 mg/day), medium (&gt; 5 and &lt; 15 mg/day), or high (≥ 15 mg/day). Results. Baseline LS, FN, and TH BMD were similar between groups, and between glucocorticoid dose categories within each group. LS BMD increases at the low, medium, and high glucocorticoid doses were 8.1%, 6.6%, and 4.6%, respectively, with teriparatide, and 3.6%, 2.8%, and 2.3% with alendronate. Analyzed as a continuous variable, higher glucocorticoid doses had a negative, but nonsignificant, effect on the percentage increase in LS BMD in both groups. Glucocorticoid dose did not significantly affect FN or TH BMD increases in either group. Across the 3 glucocorticoid dose categories, the overall LS BMD increases were different for both treatments combined (p = 0.033), but the relative differences between the treatment groups were not different (interaction, p = 0.52). Glucocorticoids effectively treat inflammatory conditions but are associated with an array of side effects 1 , including secondary osteoporosis 2 . The pathophysiology of glucocorticoid-induced osteoporosis (GIO) involves multiple mechanistic pathways, including early increases in bone resorption along with decreased bone formation, and alterations in bone microarchitecture 3 . Daily or cumulative oral glucocorticoid doses are related to decreased bone mass and the occurrence of fractures 2,4 . However, patients treated with oral glucocorticoids experience fractures at a higher bone mineral density (BMD) than patients with postmenopausal osteoporosis 5 , and the fracture risk is greater than predicted by decreased bone mass alone 6 , suggesting that glucocorticoids can also negatively affect bone quality 1,2,5 . Other mechanisms of bone fragility, such as osteocyte apoptosis and reduced repair of local defects, may contribute to the increased fracture risk observed in patients treated with chronic glucocorticoids 7 . Current guidelines for management of GIO include assessment of patients for osteoporosis risk factors prior to initiating glucocorticoid therapy, concomitant use of calcium and vitamin D supplements, and for prolonged treatment of the underlying disease, minimizing the glucocorticoid dose and/or tapering the glucocorticoid dose in low disease Conclusion

Early Effects of Abaloparatide on Bone Formation and Resorption Indices in Postmenopausal Women With Osteoporosis

Anabolic osteoporosis drugs improve bone mineral density by increasing bone formation. The objective of this study was to evaluate the early effects of abaloparatide on indices of bone formation and to assess the effect of abaloparatide on modeling-based formation (MBF), remodeling-based formation (RBF), and overflow MBF (oMBF) in transiliac bone biopsies. In this open-label, single-arm study, 23 postmenopausal women with osteoporosis were treated with 80 μg abaloparatide daily. Subjects received double fluorochrome labels before treatment and before biopsy collection at 3 months. Change in dynamic histomorphometry indices in four bone envelopes were assessed. Median mineralizing surface per unit of bone surface (MS/BS) increased to 24.7%, 48.7%, 21.4%, and 16.3% of total surface after 3 months of abaloparatide treatment, representing 5.5-, 5.2-, 2.8-, and 12.9-fold changes, on cancellous, endocortical, intracortical, and periosteal surfaces (p \u3c.001 versus baseline for all). Mineral apposition rate (MAR) was significantly increased only on intracortical surfaces. Bone formation rate (BFR/BS) was significantly increased on all four bone envelopes. Significant increases versus baseline were observed in MBF on cancellous, endocortical, and periosteal surfaces, for oMBF on cancellous and endocortical surfaces, and for RBF on cancellous, endocortical, and intracortical surfaces. Overall, modeling-based formation (MBF + oMBF) accounted for 37% and 23% of the increase in bone-forming surface on the endocortical and cancellous surfaces, respectively. Changes from baseline in serum biomarkers of bone turnover at either month 1 or month 3 were generally good surrogates for changes in histomorphometric endpoints. In conclusion, treatment with abaloparatide for 3 months stimulated bone formation on cancellous, endocortical, intracortical, and periosteal envelopes in transiliac bone biopsies obtained from postmenopausal women with osteoporosis. These increases reflected stimulation of both remodeling- and modeling-based bone formation, further elucidating the mechanisms by which abaloparatide improves bone mass and lowers fracture risk. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)