scholarly journals Effects of secukinumab on bone mineral density and bone turnover biomarkers in patients with ankylosing spondylitis: 2-year data from a phase 3 study, MEASURE 1

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jürgen Braun ◽  
Bjoern Buehring ◽  
Xenofon Baraliakos ◽  
Lianne S. Gensler ◽  
Brian Porter ◽  
...  

Abstract Background Axial spondyloarthritis including ankylosing spondylitis (AS) is characterized by chronic inflammation and new bone formation in the axial skeleton. On the other hand, bone loss, osteoporosis and an increased risk of vertebral fractures is known to frequently occur in AS. In the MEASURE 1 study, the clinically efficacious interleukin-17A inhibitor secukinumab was shown to have limited radiographic progression through 4 years in patients with active AS. Here we present a post hoc analysis to evaluate the effect of secukinumab on bone mineral density (BMD) and bone turnover biomarkers over 2 years in this study. Methods BMD was measured by dual-energy X-ray absorptiometry at the lumbar spine, total hip, and femoral neck. Spinal radiographs performed at baseline and Week 104 were assessed by modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and analyzed in relation to BMD change, considering baseline syndesmophytes. Bone turnover biomarkers were assessed at baseline and at Weeks 52 or 104. Results Among 104 patients included in this analysis, 66% were male, with a mean (SD) age of 40.4 (12.3) years. In postmenopausal women and men ≥50 years of age (T-score), the proportion of patients having normal BMD at baseline and Week 104 were 54.5%/54.5% (lumbar spine), 31.6%/55.6% (total hip), and 42.1%/44.4% (femoral neck). Similarly, at baseline, the proportion of patients with osteopenia/osteoporosis was 31.8%/13.6% (lumbar spine), 57.9%/10.5% (total hip), 42.1%/15.8% (femoral neck), and 36.4%/9.1% (lumbar spine), 44.4%/0% (total hip) and 55.6%/0% (femoral neck) at Week 104, respectively. In premenopausal women and men < 50 years of age (Z-score), the proportion of patients having BMD below the expected range for age at baseline and Week 104 were 25.0%/21.2% (lumbar spine), 11.3%/17.8% (total hip), and 9.9%/8.9% (femoral neck). In relation to mSASSS change scores ≥2 over 2 years, the increase in lumbar spine BMD was not related to radiographic progression and syndesmophyte formation. No significant changes were observed in the bone turnover markers over time. Conclusion The high proportion of AS patients with diminished BMD was confirmed in this study. An increase of BMD in the lumbar spine after 2 years of secukinumab treatment in patients with AS was found that was probably unrelated to radiographic progression. No relevant effects of secukinumab on bone turnover biomarkers were documented. Trial registration MEASURE 1 (post hoc analysis) Clinicaltrials.gov, NCT01358175; Registered, 23 May 2011.

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 &lt; 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 &lt; 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.


2017 ◽  
pp. E146-E157 ◽  
Author(s):  
Chun-Lin Liu ◽  
Han-Chung Lee ◽  
Chun-Chung Chen ◽  
Der-Yang Cho

Purpose: This meta-analysis aimed to compare the efficacy and safety of teriparatide vs. bisphosphonates in the management of osteoporosis. Methods: A total of 1,967 patients from eight randomized controlled trials were analyzed; outcomes included bone mineral density (BMD) of the femoral neck, total hip and lumbar spine, vertebral and nonvertebral fractures and any adverse event. A subgroup analysis of treatment effectiveness was performed according to the etiology of osteoporosis; i.e., glucocorticoid-induced osteoporosis (GIO) vs. post-menopausal osteoporosis (PO). Results: Teriparatide increased the BMD of the lumbar spine, femoral neck and total hip to a greater extent than bisphosphonates. Patients treated with teriparatide also had a lower risk of vertebral fractures compared with bisphosphonates; however, no difference in risk of nonvertebral fractures (or adverse events) was found. GIO subgroups showed larger increases in BMD of the lumbar spine, total hip and femoral neck in patients treated with teriparatide compared with bisphosphonates. The PO subgroup showed larger increases in BMD of the lumbar spine in patients treated with teriparatide compared with bisphosphonates. Patients in the GIO subgroup (but not the PO subgroup) were less likely to suffer a vertebral fracture on teriparatide as compared with bisphosphonates. In contrast, no significant difference in the percentage of nonvertebral fractures was noted between the two types of treatment for either subgroup. Conclusion: Teriparatide significantly increased the BMD of lumbar spine, total hip and femoral neck, particularly in GIO-induced osteoporosis. Teriparatide did not lower the risk of nonvertebral fractures when compared with bisphosphonates.


2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Chen-Xi Li ◽  
Song-Tao Tang ◽  
Qiu Zhang

To assess the prevalence of osteoporosis in young men with hypogonadotropic hypogonadism (HH) and to investigate the changes of BMD and metabolic parameters, a total of 22 young male patients with HH and 20 healthy controls were enrolled in the study. BMD, biochemical, and hormonal parameters were measured in two groups. Osteoporosis was more prevalent in HH patients (45.45%) than the control subjects (10.00%) (P<0.001). The patients with HH had lower BMD in lumbar spine 2–4, femoral neck, and total hip (P<0.001, for all) and higher fasting insulin (P=0.001), HOMA-IR (P=0.002), and SHBG (P<0.001) compared to the controls. After 6 months of pulsatile gonadorelin treatment, BMI (P=0.021) and BMD in lumbar spine 2–4, femoral neck, and total hip (P=0.002,P=0.003, andP=0.003, resp.) increased dramatically and total cholesterol (P=0.034), fasting insulin (P=0.025), HOMA-IR (P=0.021), and SHBG (P=0.001) decreased significantly in HH patients. The study shows a higher prevalence of osteoporosis in young men with HH. Long-term pulsatile gonadorelin treatment indicates a positive effect on BMD and metabolic parameters of HH patients.


Author(s):  
Dag Hofsø ◽  
Thor Olav Widerøe Hillestad ◽  
Erling Halvorsen ◽  
Farhat Fatima ◽  
Line Kristin Johnson ◽  
...  

Abstract Context Bariatric surgery, particularly Roux-en-Y gastric bypass (RYGB), is associated with an increased risk of osteoporotic fractures. It is unknown whether RYGB or sleeve gastrectomy (SG) have different effects on bone health. Objective To compare changes in bone mineral density and markers of bone turnover 1 year after SG and RYGB. Design, Setting, Patients, and Interventions Randomized, triple-blind, single-center trial at a tertiary care center in Norway. The primary outcome was diabetes remission. Patients with severe obesity and type 2 diabetes were randomized and allocated (1:1) to SG or RYGB. Main Outcome Measures Changes in areal bone mineral density (aBMD) and bone turnover markers. Results Femoral neck, total hip, and lumbar spine aBMD, but not total body aBMD, decreased significantly more after RYGB (n = 44) than after SG (n = 48) (mean [95% confidence interval] between group differences -2.8% [-4.7 to -0.8], -3.0% [-5.0 to -0.9], -4.2% [-6.4 to -2.1], and -0.5% [-1.6 to 0.6], respectively). The increase in procollagen type 1 N-terminal propeptide (P1NP) and C-telopeptide of type I collagen (CTX-1) were approximately 100% higher after RYGB than after SG (between group difference at 1 year, both P &lt; 0.001). The changes in femoral neck, total hip, and lumbar spine aBMDs and the changes in P1NP and CTX-1 were independently associated with the surgical procedure (all P &lt; 0.05) and not weight change. Conclusions Roux-en-Y gastric bypass was associated with a greater reduction in aBMD and a greater increase in bone turnover markers compared with SG. This finding could suggest greater skeletal fragility after RYGB.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marcel M. Nejatian ◽  
Salar Sobhi ◽  
Blake N. Sanchez ◽  
Kathryn Linn ◽  
Laurens Manning ◽  
...  

AbstractManagement of diabetes-related foot ulceration (DFU) includes pressure offloading resulting in a period of reduced activity. The metabolic effects of this are unknown. This study aims to investigate changes in bone mineral density (BMD) and body composition 12 weeks after hospitalisation for DFU. A longitudinal, prospective, observational study of 22 people hospitalised for DFU was conducted. Total body, lumbar spine, hip and forearm BMD, and total lean and fat mass were measured by dual-energy X-ray absorptiometry (DXA) during and 12 weeks after hospitalisation for DFU. Significant losses in total hip BMD of the ipsilateral limb (− 1.7%, p < 0.001), total hip BMD of the contralateral limb (− 1.4%, p = 0.005), femoral neck BMD of the ipsilateral limb (− 2.8%, p < 0.001) and femoral neck BMD of the contralateral limb (− 2.2%, p = 0.008) were observed after 12 weeks. Lumbar spine and forearm BMD were unchanged. HbA1c improved from 75 mmol/mol (9.2%) to 64 mmol/mol (8.0%) (p = 0.002). No significant changes to lean and fat mass were demonstrated. Total hip and femoral neck BMD decreased bilaterally 12 weeks after hospitalisation for DFU. Future research is required to confirm the persistence and clinical implications of these losses.


2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Yuta Yamaguchi ◽  
Takayoshi Morita ◽  
Atsushi Kumanogoh

Abstract Objective Prevention of steroidal osteoporosis is an important issue. There is no clear consensus on the impact of anti-RANKL antibody (denosumab) on BMD in patients with glucocorticoid-induced osteoporosis (GIO). In this study, we aimed to evaluate the impact of denosumab on BMD loss in patients with GIO. Methods A comprehensive systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. PubMed, Web of Science and Google Scholar were used to search for original studies reported about BMD in patients with GIO treated with denosumab. In meta-analysis of BMD, the mean difference in the rate of change from baseline and the 95% CI were calculated using the random effects model. The mean differences in patients treated with denosumab were compared with those in patients treated with bisphosphonates. Results Out of 713 studies identified, seven studies met the selection criteria for the meta-analysis. At 6 and 12 months of denosumab therapy, increases in BMD were observed in the lumbar spine (2.99% [95% CI 2.71, 3.28] and 4.59% [95% CI 4.17, 5.01]), total hip (1.34% [95% CI 0.64, 2.04] and 2.16% [95% CI 2.05, 2.27]) and femoral neck (0.12% [95% CI −0.38, 0.62] and 1.55% [95% CI 0.45, 2.65]). Additionally, denosumab resulted in significant increases in BMD in the lumbar spine and femoral neck at 12 months compared with bisphosphonate therapy. Conclusion Patients with GIO experienced significant increases in BMD in response to treatment with denosumab that were detected in the lumbar spine, total hip and femoral neck at 12 months.


2021 ◽  
Vol 23 (1) ◽  
pp. 45-49
Author(s):  
Chulin Chewakidakarn ◽  
Varah Yuenyongviwat

Background. Geriatric hip fractures, including femoral neck and pertrochanteric fractures, are common nowadays, which is related to increasing numbers of elderly people worldwide. Osteoporosis is an important risk factor associated with hip fractures. This study aimed to describe the association of hip fractures and osteoporosis at different BMD measurement sites and determine any differences between these two types of hip fracture. Material and methods. A retrospective study conducted in a university hospital in the south of Thailand enrolled 223 patients aged over 50 years with low-energy trauma hip fractures. Each patient had undergone dual energy x-ray absorptiometry (DXA) within 2 weeks of injury. T-scores were recorded for the total hip, femoral neck and lumbar spine areas and classified as normal, osteopenia and osteoporosis according to WHO osteoporosis diagnostic criteria. Results. The highest proportion of T-scores in the osteoporotic range were registered at the femoral neck (68.6%) compared to total hip (52.9%) and lumbar spine (47.7%). At least 31.4% of patients were in the non-osteoporotic range. No significant differences were found at all sites of BMD measurement between the two types of fracture. Conclusions. 1. At least 1/3 of patients with geriatric hip fractures had their T-scores in the normal to oste­ope­nic range. 2. BMD in different areas is not different between types of hip fractures.


2013 ◽  
Vol 98 (11) ◽  
pp. 4355-4363 ◽  
Author(s):  
Susan J. Diem ◽  
Kristine Ruppert ◽  
Jane A. Cauley ◽  
YinJuan Lian ◽  
Joyce T. Bromberger ◽  
...  

Context: Concern has been raised that medications that block serotonin reuptake may affect bone metabolism, resulting in bone loss. Objective: The aim of the study was to compare annual bone mineral density (BMD) changes among new users of selective serotonin reuptake inhibitors (SSRIs), new users of tricyclic antidepressants (TCAs), and nonusers of antidepressant medications. Design and Setting: We conducted a prospective cohort study at five clinical centers in the United States. Participants: The study included 1972 community-dwelling women, aged 42 years and older, enrolled in the Study of Women's Health Across the Nation (SWAN). Exposure: The use of antidepressant medications was assessed by interview and verified from medication containers at annual visits. Subjects were categorized as nonusers (no SSRI or TCA use at any examination), SSRI users (initiated SSRI use after the baseline SWAN visit), or TCA users (initiated TCA use after the baseline visit), using a computerized dictionary to categorize type of medication. Main Outcome Measures: BMD at the lumbar spine, total hip, and femoral neck was measured using dual-energy x-ray absorptiometry at annual visits. Results: BMD was compared among 311 new users of SSRIs, 71 new users of TCAs, and 1590 nonusers. After adjustment for potential confounders, including age, race, body mass index, menopausal status, and hormone therapy use, mean lumbar spine BMD decreased on average 0.68% per year in nonusers, 0.63% per year in SSRI users (P = .37 for comparison to nonusers), and 0.40% per year in TCA users (P = .16 for comparison to nonusers). At the total hip and femoral neck, there was also no evidence that SSRI or TCA users had an increased rate of bone loss compared with nonusers. Results were similar in subgroups of women stratified by the Center for Epidemiologic Studies Depression Scale (&lt;16 vs ≥16). Conclusions: In this cohort of middle-aged women, use of SSRIs and TCAs was not associated with an increased rate of bone loss at the spine, total hip, or femoral neck.


2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Li’nan Qin ◽  
Xiaopeng Guo ◽  
Lu Gao ◽  
Zihao Wang ◽  
Chenzhe Feng ◽  
...  

Purpose. This study analysed changes in bone mineral density (BMD) at different sites in patients with acromegaly and postoperative BMD changes and explored risk factors associated with BMD. Methods. Clinical data of 39 patients with growth hormone- (GH-) secreting pituitary adenomas and 29 patients with nonfunctioning pituitary adenomas who were newly diagnosed in neurosurgery from January 2016 to December 2018 were retrospectively analysed, including measurements of preoperative and postoperative BMD, serum GH glucose inhibition, random GH and IGF-1, and other anterior pituitary hormones. Results. The average patient age and disease duration were 43.74 (33.41–54.07) years and 72.15 (22.82–121.48) months, respectively. Compared with patients with nonfunctioning adenomas, patients with GH-secreting pituitary adenomas had significantly higher BMDs at L1, L2, femoral neck, Ward triangle, trochanter, femoral shaft, and total hip sites (p<0.05). The BMD Z score at L1 and femoral neck sites significantly increased (p<0.05). Thirteen patients underwent re-examination of BMD 1 year postsurgery, and the BMD Z score was reduced to normal levels at L1, L2, L3, L4, L1-L4, and L2-L4 compared with preoperative levels (p<0.05). Postoperative BMD Z scores in the femoral neck and total hip were significantly increased (p<0.05). Disease duration was negatively correlated with the lumbar-spine BMD Z score. IGF-1 burden was negatively correlated with the BMD Z score at L1 and L1–L4. Multiple regression analysis showed that IGF-1 burden was a risk factor for a BMD Z score decrease at L1 and L1–L4. Conclusion. BMD in patients with GH-secreting pituitary adenomas (compared with nonfunctional adenomas) increased at L1, L2, femoral neck, Ward triangle, trochanter, femoral shaft, and total hip sites. Lumbar-spine BMD Z score recovered to normal levels postsurgically when GH and IGF-1 levels were controlled. BMD Z score was negatively correlated with disease duration and IGF-1 burden in patients with GH-secreting pituitary adenomas, and IGF-1 burden was an independent risk factor for reduced lumbar-spine BMD Z score.


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