scholarly journals Effects of Previous Antiresorptive Therapy on the Bone Mineral Density Response to Two Years of Teriparatide Treatment in Postmenopausal Women with Osteoporosis

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.

2008 ◽  
Vol 26 (7) ◽  
pp. 1051-1057 ◽  
Author(s):  
Richard Eastell ◽  
Judith E. Adams ◽  
Robert E. Coleman ◽  
Anthony Howell ◽  
Rosemary A. Hannon ◽  
...  

Purpose The Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial (median follow-up, 68 months) has shown that adjuvant anastrozole has superior efficacy and better tolerability than tamoxifen. However, anastrozole reduces circulating estrogen, and low estradiol levels are associated with decreased bone mineral density (BMD) and increased fracture risk. It is therefore important to understand the effects of long-term aromatase inhibitor therapy on BMD. Patients and Methods This prospective substudy of the ATAC trial assessed BMD changes in postmenopausal women with invasive primary breast cancer receiving anastrozole (1 mg/d) or tamoxifen (20 mg/d) as adjuvant therapy for 5 years. Lumbar spine and total hip BMD were assessed at baseline and after 1, 2, and 5 years. Results One hundred ninety-seven women from the monotherapy arms of the ATAC trial were recruited onto the bone substudy, and 108 were included in the primary analysis. Among anastrozole-treated patients, there was a decrease in median BMD from baseline to 5 years in lumbar spine (−6.08%) and total hip (−7.24%) compared with the tamoxifen group (lumbar spine, +2.77%; total hip, +0.74%). No patients with normal BMD at baseline became osteoporotic at 5 years. Conclusion Anastrozole is associated with accelerated bone loss over the 5-year treatment period. However, although patients with pre-existing osteopenia are likely to require monitoring and bone-protection strategies, patients with normal BMD would not appear to require monitoring beyond the recommendation for healthy postmenopausal women. The effect of anastrozole on bone should be weighed against its superior efficacy and better tolerability profile versus tamoxifen in the main ATAC trial.


2017 ◽  
Author(s):  
Wenjia Chen ◽  
Kate M. Johnson ◽  
J. Mark FitzGerald ◽  
Mohsen Sadatsafavi ◽  
William D. Leslie

ABSTRACTBackgroundThe effect of long-term inhaled corticosteroid (ICS) therapy on the bone health of older adults remains unclear due to its possible impact on bone mineral density (BMD).ObjectiveTo evaluate, cross-sectionally and longitudinally, the impact of ICS use on BMD in postmenopausal women with asthma or chronic obstructive pulmonary disease (COPD).MethodsWe used a population-based bone densitometry registry linked with administrative health data of the province of Manitoba, Canada (1999–2013), to identify women with diagnosed asthma or COPD. ICS use was defined as cumulative dispensed days prior to baseline BMD (cross-sectional analysis), and medication possession ratio (MPR) between two BMD measurements (longitudinal analysis). Results were adjusted for multiple covariates including the underlying respiratory diagnosis and its severity.ResultsIn the cross sectional analysis, compared with non-users, women with the highest tertile of prior ICS exposure had lower baseline BMD at the femoral neck (-0.09 standard deviations [SD] below a healthy young adult, 95% CI: −0.16, −0.02) and total hip (-0.14 SD, 95% CI: −0.22, −0.05), but not at the lumbar spine. Longitudinally, the highest tertile of ICS exposure was associated with a slight decline in total hip BMD relative to non-users (-0.02 SD/year, 95% CI: −0.04, −0.01), with no significant effect at the femoral neck and lumbar spine. Middle and lower tertiles of ICS use had no significant effects.ConclusionHigh exposure to ICS was associated with a small adverse effect on baseline hip BMD and total hip BMD loss in post-menopausal women with asthma or COPD.


2009 ◽  
Vol 94 (10) ◽  
pp. 3772-3780 ◽  
Author(s):  
Felicia Cosman ◽  
Robert A. Wermers ◽  
Christopher Recknor ◽  
Karen F. Mauck ◽  
Li Xie ◽  
...  

Objective: The aim of the study was to assess adding vs. switching to teriparatide 20μg/d in patients on alendronate or raloxifene. Design: We conducted a randomized, open-label trial. Patients and Interventions: Postmenopausal women with osteoporosis on alendronate or raloxifene for at least 18 months added teriparatide (Add groups) or switched to teriparatide (Switch groups) for 18 months. Main Outcome Measures: We measured bone turnover markers (BTM) and bone mineral density (BMD). Results: In the alendronate stratum, increases in BTM were smaller in the Add vs. Switch group [6-month PINP (64 vs. 401%); bone ALP (15 vs. 71%); βCTX (27 vs. 250%); all P < 0.001]. However, at 6 months, total hip BMD increased more in the Add vs. Switch group (1.4 vs. −0.8%; P = 0.002). In the Add vs. Switch group, 18-month BMD increments were higher in lumbar spine (8.4 vs. 4.8%; P = 0.003) and total hip (3.2 vs. 0.9%; P = 0.02), but not in femoral neck (2.7 vs. 2.3%; P = 0.75). In the raloxifene stratum, increases in BTM were also smaller in the Add vs. Switch group [6-month PINP (131 vs. 259%; P < 0.001), bone ALP (31 vs. 44%; P = 0.035), and βCTX (67 vs. 144%; P = 0.001)]. At 6 months, total hip BMD increase was greater in the Add vs. Switch group (1.8 vs. 0.5%; P = 0.028). At 18 months, increases in lumbar spine (9.2 vs. 8.1%), total hip (2.8 vs. 1.8%), and femoral neck (3.8 vs. 2.2%) were not significantly different between groups. Conclusions: In women with osteoporosis treated with antiresorptives, greater bone turnover increases were achieved by switching to teriparatide, whereas greater BMD increases were achieved by adding teriparatide. In patients treated with alendronate or raloxifene, adding teriparatide results in a greater bone mineral density response, and appears to be at least as safe as switching to teriparatide.


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.


2012 ◽  
Vol 97 (11) ◽  
pp. 4061-4070 ◽  
Author(s):  
Antonia Hoeg ◽  
Apostolos Gogakos ◽  
Elaine Murphy ◽  
Sandra Mueller ◽  
Josef Köhrle ◽  
...  

Context: Selenium status may have direct effects on bone and indirect effects through changes in thyroid hormone sensitivity. Objective: We hypothesized that variation in selenium status in healthy euthyroid postmenopausal women is associated with differences in bone turnover, bone mineral density (BMD) and fracture susceptibility. Design: The Osteoporosis and Ultrasound Study (OPUS) is a 6-yr prospective study of fracture-related factors. Setting: The study was comprised of a population-based cohort from five European cities. Participants: A total of 2374 postmenopausal women participated. Subjects with thyroid disease and nonthyroidal illness and those receiving drugs affecting thyroid status or bone metabolism were excluded, leaving a study population of 1144. Interventions: There were no interventions. Main Outcome Measures: We measured selenium (micrograms per liter); selenoprotein P (milligrams per liter); free T4 (picomoles per liter); free T3 (picomoles per liter); TSH (milliunits per liter); bone turnover markers; BMD; and vertebral, hip, and nonvertebral fractures. Results: Higher selenium levels were associated with higher hip BMD at study entry (β = 0.072, P = 0.004) and lower levels of bone formation (osteocalcin: β = −0.101, P < 0.001; procollagen type 1 N-terminal propeptide: β = −0.074, P = 0.013) and resorption markers (C-telopeptide of type 1 collagen: β = −0.058, P = 0.050; N-telopeptide of type 1 collagen: β = −0.095, P = 0.002). Higher selenoprotein P was associated with higher hip (β = 0.113, P < 0.001) and lumbar spine BMD (β = 0.088, P = 0.003) at study entry, higher hip BMD after the 6-yr follow-up (β = 0.106, P = 0.001) and lower osteocalcin (β = −0.077, P = 0.009), C-telopeptide of type 1 collagen (β = −0.075, P = 0.012), and N-telopeptide of type 1 collagen (β = −0.110, P < 0.001). Conclusion: Selenium status is inversely related to bone turnover and positively correlated with BMD in healthy euthyroid postmenopausal women independent of thyroid status.


2020 ◽  
Vol 14 ◽  
pp. 175346662096514
Author(s):  
Francois Maltais ◽  
Isabelle Schenkenberger ◽  
Pascal L. M. L. Wielders ◽  
Juan Ortiz de Saracho ◽  
Kenneth Chinsky ◽  
...  

Background: The relationship between inhaled corticosteroids and bone mineral density (BMD) remains uncertain despite extensive research. Methods: This was an international, multicenter, randomized, double-blind, parallel-group, 3-year noninferiority study. Patients with chronic obstructive pulmonary disease (COPD) (⩾40 years of age; smoking history ⩾10 pack years) and at least one native hip evaluable for BMD were enrolled and randomized 1:1, stratified by sex, to treatment with vilanterol (VI) 25 µg or fluticasone furoate/vilanterol (FF/VI) 100 µg/25 µg. BMD measurements were taken via dual-energy X-ray absorptiometry every 6 months. The primary endpoint was assessment of the noninferiority of change from baseline in total hip BMD per year at the −1% noninferiority level. Change from baseline in BMD at the lumbar spine and BMD measurements by sex were secondary endpoints. Incidences of COPD exacerbations and bone fractures throughout the study were also recorded. Results: Of 283 randomized patients, 170 (60%) completed the study. Noninferiority was demonstrated for FF/VI versus VI with regards to change from baseline in total hip BMD per year, with changes of −0.27% and 0.18%, respectively, and a treatment difference of −0.46% per year [95% confidence interval (CI) −0.97 to 0.06]. The treatment difference for FF/VI versus VI regarding lumbar spine BMD was −0.51% per year (95% CI −1.11 to 0.10). COPD exacerbations and bone fracture rates were similar between treatment groups. Conclusion: FF/VI showed noninferiority to VI for change from baseline in total hip BMD per year, when assessed at the −1% noninferiority margin in a combined sample of men and women with COPD. The reviews of this paper are available via the supplemental material section.


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.


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.


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