scholarly journals Bone Density, Turnover, and Estimated Strength in Postmenopausal Women Treated With Odanacatib: A Randomized Trial

2013 ◽  
Vol 98 (2) ◽  
pp. 571-580 ◽  
Author(s):  
Kim Brixen ◽  
Roland Chapurlat ◽  
Angela M. Cheung ◽  
Tony M. Keaveny ◽  
Thomas Fuerst ◽  
...  

Abstract Context: Odanacatib, a cathepsin K inhibitor, increases spine and hip areal bone mineral density (BMD) in postmenopausal women with low BMD and cortical thickness in ovariectomized monkeys. Objective: The objective of the study was to examine the impact of odanacatib on the trabecular and cortical bone compartments and estimated strength at the hip and spine. Design: This was a randomized, double-blind, 2-year trial. Setting: The study was conducted at a private or institutional practice. Participants: Participants included 214 postmenopausal women with low areal BMD. Intervention: The intervention included odanacatib 50 mg or placebo weekly. Main Outcome Measures: Changes in areal BMD by dual-energy x-ray absorptiometry (primary end point, 1 year areal BMD change at lumbar spine), bone turnover markers, volumetric BMD by quantitative computed tomography (QCT), and bone strength estimated by finite element analysis were measured. Results: Year 1 lumbar spine areal BMD percent change from baseline was 3.5% greater with odanacatib than placebo (P < .001). Bone-resorption marker C-telopeptide of type 1 collagen was significantly lower with odanacatib vs placebo at 6 months and 2 years (P < .001). Bone-formation marker procollagen I N-terminal peptide initially decreased with odanacatib but by 2 years did not differ from placebo. After 6 months, odanacatib-treated women had greater increases in trabecular volumetric BMD and estimated compressive strength at the spine and integral and trabecular volumetric BMD and estimated strength at the hip (P < .001). At the cortical envelope of the femoral neck, bone mineral content, thickness, volume, and cross-sectional area also increased from baseline with odanacatib vs placebo (P < .001 at 24 months). Adverse experiences were similar between groups. Conclusions: Over 2 years, odanacatib decreased bone resorption, maintained bone formation, increased areal and volumetric BMD, and increased estimated bone strength at both the hip and spine.

2008 ◽  
Vol 93 (3) ◽  
pp. 852-860 ◽  
Author(s):  
Steven Boonen ◽  
Fernando Marin ◽  
Barbara Obermayer-Pietsch ◽  
Maria E. Simões ◽  
Clare Barker ◽  
...  

Abstract Introduction: EUROFORS was a 2-yr prospective, randomized trial of postmenopausal women with established osteoporosis, designed to investigate various sequential treatments after teriparatide 20 μg/d for 1 yr. The present secondary analysis examined the effects of 2 yr of open-label teriparatide in women previously treated with antiresorptive drugs for at least 1 yr. Methods: A subgroup of 245 women with osteoporosis who had 2 yr of teriparatide treatment were stratified by previous predominant antiresorptive treatment into four groups: alendronate (n = 107), risedronate (n = 59), etidronate (n = 30), and non-bisphosphonate (n = 49). Bone mineral density (BMD) at the lumbar spine and hip was determined after 6, 12, 18, and 24 months, and bone formation markers were measured after 1 and 6 months. Results: Significant increases in bone formation markers occurred in all groups after 1 month of teriparatide treatment. Lumbar spine BMD increased at all visits, whereas a transient decrease in hip BMD, which was subsequently reversed, was observed in all groups. BMD responses were similar in all previous antiresorptive groups. Previous etidronate users showed a higher increase at the spine but not at the hip BMD. Duration of previous antiresorptive therapy and lag time between stopping previous therapy and starting teriparatide did not affect the BMD response at any skeletal site. Treatment-emergent adverse events were similar to those reported in treatment-naive postmenopausal women with osteoporosis treated with teriparatide. Conclusions: Teriparatide induces positive effects on BMD and markers of bone formation in postmenopausal women with established osteoporosis, regardless of previous long-term exposure to antiresorptive therapies.


2014 ◽  
Vol 13 (1) ◽  
pp. 8-15 ◽  
Author(s):  
E. N. Dudinskaya ◽  
O. N. Tkacheva

Aim. To assess the effects of moxonidine in terms of target blood pressure (BP) achievement; to identify potential additional benefits of moxonidine and its effects on bone metabolism and bone mineral density (BMD) in postmenopausal women with arterial hypertension (AH).Material and methods. The study included 48 postmenopausal women with Stage 1-2 AH, aged 57-71 years.Results. All participants were divided into two groups by the type of antihypertensive therapy: those receiving moxonidine and those receiving angiotensin-converting enzyme inhibitors / angiotensin receptor antagonists (ACEI/ARA). All women also received calcium and vitamin D. All participants had AH and osteopenia (both in the lumbar spine and proximal femur, according to the X-ray absorptiometry results). In the moxonidine group, BP levels remained within the target range 48 weeks later. There was a significant reduction in the levels of a bone resorption marker (p=0,041), while the dynamics of an osteopoetic marker was statistically non-significant (p=0,31). A tendency towards increasing BMD in lumbar spine and proximal femur was also observed (p=0,059 and p=0,068, respectively). In the ACEI/ARA group, BP levels also remained within the target range 48 weeks later. However, no significant changes in the levels of bone metabolism markers were registered. There was a tendency towards decreasing BMD in lumbar spine and proximal femur (p=0,052 and p=0,054, respectively).Conclusion. Moxonidine therapy was associated with a significant reduction in bone resorption activity, as demonstrated by the decrease in the concentration of a bone resorption marker, as well as with a tendency towards increasing BMD.


2002 ◽  
Vol 87 (10) ◽  
pp. 4528-4535 ◽  
Author(s):  
Jean-Jacques Body ◽  
Gregory A. Gaich ◽  
Wim H. Scheele ◽  
Pandurang M. Kulkarni ◽  
Paul D. Miller ◽  
...  

Teriparatide (rDNA origin) injection [recombinant human PTH (1–34)] stimulates bone formation, increases bone mineral density (BMD), and restores bone architecture and integrity. In contrast, bisphosphonates reduce bone resorption and increase BMD. We compared the effects of teriparatide and alendronate sodium on BMD, nonvertebral fracture incidence, and bone turnover in 146 postmenopausal women with osteoporosis. Women were randomized to either once-daily sc injections of teriparatide 40 μg plus oral placebo (n = 73) or oral alendronate 10 mg plus placebo injection (n = 73). Median duration of treatment was 14 months. At 3 months, teriparatide increased lumbar spine BMD significantly more than did alendronate (P < 0.001). Lumbar spine-BMD increased by 12.2% in the teriparatide group and 5.6% in the alendronate group (P < 0.001 teriparatide vs. alendronate). Teriparatide increased femoral neck BMD and total body bone mineral significantly more than did alendronate, but BMD at the one third distal radius decreased, compared with alendronate (P ≤ 0.05). Nonvertebral fracture incidence was significantly lower in the teriparatide group than in the alendronate group (P < 0.05). Both treatments were well tolerated despite transient mild asymptomatic hypercalcemia with teriparatide treatment. In conclusion, teriparatide, a bone formation agent, increased BMD at most sites and decreased nonvertebral fractures more than alendronate.


2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
A. Sánchez ◽  
L. R. Brun ◽  
H. Salerni ◽  
P. R. Costanzo ◽  
D. González ◽  
...  

The aim of this study was to evaluate the effect of denosumab (Dmab) on bone mineral density (BMD) and bone turnover markers after 1 year of treatment. Additionally, the effect of Dmab in bisphosphonate-naïve patients (BP-naïve) compared to patients previously treated with bisphosphonates (BP-prior) was analyzed. This retrospective study included 425 postmenopausal women treated with Dmab for 1 year in clinical practice conditions in specialized centers from Argentina. Participants were also divided according to previous bisphosphonate treatment into BP-naïve and BP-prior. A control group of patients treated with BP not switched to Dmab matched by sex, age, and body mass index was used. Data are expressed as mean ± SEM. After 1 year of treatment with Dmab the bone formation markers total alkaline phosphatase and osteocalcin were significantly decreased (23.36% and 43.97%, resp.), as was the bone resorption marker s-CTX (69.61%). Significant increases in BMD were observed at the lumbar spine, femoral neck, and total hip without differences between BP-naïve and BP-prior. A better BMD response was found in BP-prior group compared with BP treated patients not switched to Dmab.Conclusion. Dmab treatment increased BMD and decreased bone turnover markers in the whole group, with similar response in BP-naïve and BP-prior patients. A better BMD response in BP-prior patients versus BP treated patients not switched to Dmab was observed.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Stefana Catalina Bilha ◽  
Letitia Leustean ◽  
Cristina Preda ◽  
Dumitru D. Branisteanu ◽  
Laura Mihalache ◽  
...  

Abstract Background Despite the increased fracture risk, bone mineral density (BMD) is variable in type 1 (T1D) and type 2 (T2D) diabetes mellitus. We aimed at comparing independent BMD predictors in T1D, T2D and control subjects, respectively. Methods Cross-sectional case-control study enrolling 30 T1D, 39 T2D and 69 age, sex and body mass index (BMI) – matched controls that underwent clinical examination, dual-energy X-ray absorptiometry (BMD at the lumbar spine and femoral neck) and serum determination of HbA1c and parameters of calcium and phosphate metabolism. Results T2D patients had similar BMD compared to T1D individuals (after adjusting for age, BMI and disease duration) and to matched controls, respectively. In multiple regression analysis, diabetes duration – but not HbA1c- negatively predicted femoral neck BMD in T1D (β= -0.39, p = 0.014), while BMI was a positive predictor for lumbar spine (β = 0.46, p = 0.006) and femoral neck BMD (β = 0.44, p = 0.007) in T2D, besides gender influence. Age negatively predicted BMD in controls, but not in patients with diabetes. Conclusions Long-standing diabetes and female gender particularly increase the risk for low bone mass in T1D. An increased body weight partially hinders BMD loss in T2D. The impact of age appears to be surpassed by that of other bone regulating factors in both T1D and T2D patients.


2018 ◽  
Vol 238 (1) ◽  
pp. 13-23 ◽  
Author(s):  
Thomas Funck-Brentano ◽  
Karin H Nilsson ◽  
Robert Brommage ◽  
Petra Henning ◽  
Ulf H Lerner ◽  
...  

WNT signaling is involved in the tumorigenesis of various cancers and regulates bone homeostasis. Palmitoleoylation of WNTs by Porcupine is required for WNT activity. Porcupine inhibitors are under development for cancer therapy. As the possible side effects of Porcupine inhibitors on bone health are unknown, we determined their effects on bone mass and strength. Twelve-week-old C57BL/6N female mice were treated by the Porcupine inhibitors LGK974 (low dose = 3 mg/kg/day; high dose = 6 mg/kg/day) or Wnt-C59 (10 mg/kg/day) or vehicle for 3 weeks. Bone parameters were assessed by serum biomarkers, dual-energy X-ray absorptiometry, µCT and histomorphometry. Bone strength was measured by the 3-point bending test. The Porcupine inhibitors were well tolerated demonstrated by normal body weight. Both doses of LGK974 and Wnt-C59 reduced total body bone mineral density compared with vehicle treatment (P < 0.001). Cortical thickness of the femur shaft (P < 0.001) and trabecular bone volume fraction in the vertebral body (P < 0.001) were reduced by treatment with LGK974 or Wnt-C59. Porcupine inhibition reduced bone strength in the tibia (P < 0.05). The cortical bone loss was the result of impaired periosteal bone formation and increased endocortical bone resorption and the trabecular bone loss was caused by reduced trabecular bone formation and increased bone resorption. Porcupine inhibitors exert deleterious effects on bone mass and strength caused by a combination of reduced bone formation and increased bone resorption. We suggest that cancer targeted therapies using Porcupine inhibitors may increase the risk of fractures.


2005 ◽  
Vol 46 (3) ◽  
pp. 269-275 ◽  
Author(s):  
G. Guglielmi ◽  
I. Floriani ◽  
V. Torri ◽  
J. Li ◽  
C. van Kuijk ◽  
...  

Purpose: To evaluate the impact of degenerative changes due to osteoarthritis (OA) at the spine on volumetric bone mineral density (BMD) as measured by volumetric quantitative computed tomography (vQCT). Material and Methods: Eighty‐four elderly women (mean age 73±6 years), comprising 33 with vertebral fractures assessed by radiographs and 51 without vertebral fractures, were studied. Trabecular, cortical, and integral BMD were examined at the spine and hip using a helical CT scanner and were compared to dual X‐ray absorptiometry (DXA) measurements at the same sites. OA changes visible on the radiographs were categorized into two grades according to severity. Differences in BMD measures obtained in the two groups of patients defined by OA grade using the described radiologic methods were compared using analysis of variance. Standardized difference (effect sizes) was also compared between radiologic methods. Results: Spinal trabecular BMD did not differ significantly between OA grade 0 and OA grade 1. Spinal cortical and integral BMD measures showed statistically significant differences, as did the lumbar spine DXA BMD measurement (13%, P = 0.02). The QCT measurements at the hip were also higher in OA 1 subjects. Femoral trabecular BMD was 13–15% higher in OA grade 1 subjects than in OA grade 0 subjects. The cortical BMD measures in the CT_TOT_FEM and CT_TROCH ROI's were also higher in the OA 1 subjects. The integral QCT BMD measures in the hip showed difference between grades OA 1 and 0. The DXA measurements in the neck and trochanter ROI's showed smaller differences (9 and 11%, respectively). There were no statistically significant differences in bone size. Conclusion: There is no evidence supporting that trabecular BMD measurements by QCT are influenced by OA. Instead, degenerative changes have an effect on both cortical and integral QCT, and on DXA at the lumbar spine and the hip. For subjects with established OA, assessment of BMD by volumetric QCT may be suggested.


2014 ◽  
Vol 7 ◽  
pp. CMED.S15086 ◽  
Author(s):  
Helisane Lima ◽  
Juliana Maia ◽  
Francisco Bandeira

Objective To evaluate the responses of C-terminal telopeptide (CTX) and serum osteocalcin after the first 4 months of treatment with strontium ranelate (SR) and demonstrate their association with long-term bone density changes. Subjects and Methods A sample of 13 postmenopausal women with osteoporosis was analyzed (mean age 65 ± 7.7 years), who were treated with SR for an average of 2.56 ± 0.86 years. All patients had undergone previous treatment with bisphosphonates for an average period of 4.88 ± 2.27 years. Serum CTX and osteocalcin levels were determined before and after four months of treatment with SR. Bone mineral density in the lumbar spine and femoral neck were obtained before and after treatment with SR. Results We observed an average increase of 53.7% in the CTX levels, and 30.7% in the osteocalcin levels. The increase in bone markers was associated with a mean 4.8% increase in lumbar spine bone mineral density (BMD) from 0.820 to 0.860 g/cm2 ( T-score from –2.67 to –1.92; P= 0.001), after 2.5 years of treatment with SR. Conclusion These data suggest an anabolic effect of SR on postmenopausal women who were previously treated with long-term bisphosphonates.


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