scholarly journals Efficacy of Romosozumab for Osteoporosis in a Patient With Osteogenesis Imperfecta: A Case Report

Author(s):  
Masashi Uehara ◽  
Yukio Nakamura ◽  
Masaki Nakano ◽  
Akiko Miyazaki ◽  
Takako Suzuki ◽  
...  

ABSTRACT The efficacy of romosozumab for severe osteoporosis is uncertain in patients with osteogenesis imperfecta (OI). This report introduced a severe osteoporotic case of OI to examine the effect of romosozumab on bone fragility. A 64-year-old man with OI was referred to our department for finding out the cause of his repeated fractures. He was medicated with alendronate for only one year, eight years ago, but it did not prevent repeated fractures, and thus he had not received any treatments for osteoporosis since then. However, recently, the frequency of fractures had become increased. At presentation, his lumbar and bilateral total hip bone mineral density (BMD) values were severely decreased at 0.546 and 0.209 g/cm2, respectively. Because of his severe osteoporosis, we started romosozumab treatment with eldecalcitol. Romosozumab (210 mg) was injected subcutaneously every month. At 12 months after drug initiation, his lumbar and total hip BMD increased by 22.0% and 136.4% versus pre-treatment levels, respectively. Bone formation markers increased, and bone resorption markers decreased at 12 months of the therapy. Neither hypocalcemia nor any other severe adverse effects were observed in this severe osteoporotic case. This study revealed good responses of BMD and bone turnover markers to romosozumab treatment, which can be considered as an effective treatment option for osteoporotic OI patients.

2020 ◽  
Vol 33 (11) ◽  
pp. 1391-1397
Author(s):  
Daisuke Harada ◽  
Hiroko Kashiwagi ◽  
Kaoru Ueyama ◽  
Kyoko Oriyama ◽  
Yuki Hanioka ◽  
...  

AbstractObjectivesOsteogenesis imperfecta (OI) is a skeletal dysplasia characterized by recurrent fractures due to congenital bone fragility. The only bisphosphonate approved for OI in Japan is pamidronate (PAM). To investigate whether monthly intravenous alendronate (ALN) infusions can maintain bone strength in OI children following cyclical PAM treatment.MethodsA prospective and non-inferiority study was conducted. Eight school-age OI patients aged 8.5±2.0 years who were treated with cyclical PAM for 6.0±2.3 years were enrolled and switched to monthly intravenous ALN (0.030 mg/kg/month). Changes in L1-4 bone mineral density (BMD) Z-scores, fracture rates, and bone turnover markers for 12 months were analyzed.ResultsAverage BMD Z-scores were −3.0±1.9, −2.9±2.0, and −2.2±2.0 in 12 months before enrollment, at enrollment, and after 12 months of ALN treatment, respectively. BMD Z-scores increased significantly during treatment with both PAM and ALN (p=0.012), and the effect of ALN was not inferior to that of PAM (p=0.67). There was no change in fracture rates (p=0.86) and bone turnover markers during the 12 months before and after enrollment. Additionally, ALN showed no remarkable side effects.ConclusionsOur results suggest that monthly intravenous ALN can maintain bone strength after primary usage of cyclical PAM. We concluded that monthly intravenous ALN as a maintenance treatment following cyclical PAM administration can be an option for OI children.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 836.2-837
Author(s):  
M. Rato ◽  
F. Oliveira Pinheiro ◽  
S. Garcia ◽  
B. M. Fernandes ◽  
D. Fonseca ◽  
...  

Background:Treatment with teriparatide (TPTD) is associated with reduction of fracture risk in patients with severe osteoporosis. This drug can only be used for up to 2 years. After that a treatment course with antiresorptives should be considered, in order to prevent the rebound of bone turnover observed after TPTD discontinuation. In this regard, interest in sequential osteoporosis therapy has grown in recent years but the ideal timing for starting another treatment after TPTD is not well established.Objectives:The aim of this study is to assess if the timing of onset of antiresorptive therapy after TPTD discontinuation has implications in total hip bone mineral density (BMD) and in fracture risk.Methods:We performed a retrospective cohort study that included patients with severe osteoporosis treated with TPTD 20mcg/day for 24 months and followed for at least 2 more years in the rheumatology department of a tertiary university hospital. For analysis, demographic and clinical data and results of dual-energy X-ray absorptiometry (DXA) after cessation of teriparatide were used. For comparison between groups Mann-Whitney U test was used.Results:Fifty-five patients with osteoporosis, with a median age of 68 (32-85) years, were included. Forty-nine patients were female (89.1%). Nineteen patients (34.5%) had primary osteoporosis and 36 (65.5%) glucocorticoid-induced osteoporosis. The median time for initiating antiresorptive treatment was 7 (0-35) months after cessation of TPTD. Forty-three patients (78.2%) started a bisphosphonate, 6 denosumab (10.9%) and 6 patients did not receive any other treatment. The most prescribed bisphosphonate was zoledronate (69.8%). All patients received calcium and vitamin D supplementation. After completion of TPTD regimen 8 patients experienced at least one fragility fracture (14.5%). At follow-up, 37 (67.3%) of patients underwent DXA on average 30.0±15.4 months after starting antiresorptive agents. The median total hip BMD in patients who started antiresorptive therapy in the first 12 months (inclusive) after cessation of TPTD regime was 0,738 (0.587-0.993) g/cm2 and the median total hip BMD of patients who started therapy after one year of discontinuation of TPTD was 0.683 (0.390-0.813) g/cm2. This difference is marginally significant (p=0.067). The median time in starting antiresorptive treatment is higher in patients with new fragility fractures after TPTD than in patients without new fractures however this difference was not statistically significant (10.0 [2-35] vs 6.0 [0-35] months; p=0.393, respectively).Conclusion:Although this study is unable to show that anti-resorptive treatment should be started in the first year after discontinuation of TPTD, it is promising since the difference between the medians in the total hip BMD values obtained until one year and after one year are marginally significant. These results can be linked to the small sample size and highlight the need for further studies in this area.References:[1]Napoli N, Langdahl BL, Ljunggren Ö, Lespessailles E, Kapetanos G, Kocjan T, Nikolic T, Eiken P, Petto H, Moll T, Lindh E, Marin F. Effects of Teriparatide in Patients with Osteoporosis in Clinical Practice: 42-Month Results During and After Discontinuation of Treatment from the European Extended Forsteo® Observational Study (ExFOS). Calcif Tissue Int. 2018 Oct;103(4):359-371. doi: 10.1007/s00223-018-0437-x. Epub 2018 Jun 16. PMID: 29909449; PMCID: PMC6153867.Disclosure of Interests:None declared.


2021 ◽  
Vol 33 (1) ◽  
Author(s):  
Yuthasak Peerakul ◽  
Jirapong Leeyaphan ◽  
Karn Rojjananukulpong

Abstract Background The prevalence of osteoporosis in patients who undergo a primary total knee arthroplasty (TKA) is increasing. Low bone mineral density (BMD) is related to unfavorable outcomes following TKA such as migration of uncemented tibial components. Postoperative blood loss in TKA is an important complication. Non-modifying predicting factors for postoperative blood loss in patients undergoing primary TKA need further elucidation. Studies on the association between BMD and blood loss after TKA are limited. We aimed to demonstrate the relationship between BMD and postoperative drainage volume following primary TKA. Methods A cross-sectional study was conducted between January 2014 and August 2020. A total of 119 primary varus osteoarthritis knees with BMD results were included in the study. Patients with secondary causes of osteoporosis were excluded. Results The median postoperative drainage volume of participants in the normal total hip BMD group and the normal trochanter BMD group was higher than that of patients in the low total hip BMD group and the low trochanter BMD group (285.0 ml vs 230.0 ml, P = 0.003; 282.5 ml vs 240.0 ml, P = 0.013, respectively). Multivariate regression analyses showed that operative time, spinal anesthesia, and normal total hip BMD status were significant predictive factors associated with increased postoperative drainage volume (P = 0.014, 0.022, and 0.013, respectively). No association was identified between the lumbar spine BMD status and postoperative drainage volume. Conclusions The relationship between BMD and postoperative blood loss in primary TKA was identified in this study. Normal total hip BMD was found to be associated with an increased postoperative drainage volume after primary TKA compared with low BMD.


Author(s):  
Chin Yi Chan ◽  
Shaanthana Subramaniam ◽  
Norazlina Mohamed ◽  
Norliza Muhammad ◽  
Fitri Fareez Ramli ◽  
...  

Background: The currently available bone turnover markers are mostly derived from osteoblasts or osteoclasts. Protein markers derived from osteocytes, the most abundant bone cells that can regulate bone turnover activities by other cells, are less explored. Objective: This study aimed to compare the circulating markers of osteocytes and calcium homeostasis between Malaysian postmenopausal women with and without osteoporosis. Method: Postmenopausal women with (n=20) or without osteoporosis (n=20) as determined by dual-energy X-ray absorptiometry were randomly drawn from a bone health cohort. Their fasting blood was collected and assayed by a multiplex immunoassay panel. Results: The results showed that osteoprotegerin and sclerostin levels were significantly lower among postmenopausal women with osteoporosis than the normal control. No significant differences in other markers were observed between the two groups. Sclerostin level correlated positively with spine bone mineral density (BMD), while 25-hydroxyvitamin D correlated negatively with hip BMD in the control group. No significant correlation was observed between other markers with spine or hip BMD. Conclusion: These data provide an insight into the possible roles of osteocyte markers, especially osteoprotegerin and sclerostin in classifying subjects with osteoporosis. However, the lack of association between these markers and BMD indicates that osteoporosis is a complex and multifactorial condition.


2019 ◽  
Vol 104 (11) ◽  
pp. 5611-5620 ◽  
Author(s):  
Houchen Lyu ◽  
Sizheng S Zhao ◽  
Kazuki Yoshida ◽  
Sara K Tedeschi ◽  
Chang Xu ◽  
...  

Abstract Context Teriparatide and denosumab are effective treatments for osteoporosis and typically reserved as second-line options after patients have used bisphosphonates. However, limited head-to-head comparative effectiveness data exist between teriparatide and denosumab. Objective We compared changes in bone mineral density (BMD) between groups treated with teriparatide or denosumab after using bisphosphonates, focusing on the change in BMD while on either drug over 2 years. Design Observational cohort study using electronic medical records from two academic medical centers in the United States. Participants The study population included osteoporotic patients >45 years who received bisphosphonates >1 year before switching to teriparatide or denosumab. Outcome Measures Annualized BMD change from baseline at the lumbar spine, total hip, and femoral neck. Results Patients treated with teriparatide (n = 110) were compared with those treated with denosumab (n = 105); the mean (SD) age was 70 (10) years and median duration (interquartile range) of bisphosphonate use was 7.0 (5.6 to 9.7) years. Compared with denosumab users, teriparatide users had higher annualized BMD change at the spine by 1.3% (95% CI 0.02, 2.7%) but lower at the total hip by −2.2% (95% CI −2.9 to −1.5%) and the femoral neck by −1.1% (95% CI −2.1 to −0.1%). Those who switched to teriparatide had a transient loss of hip BMD for the first year, with no overall increase in the total hip BMD over 2 years. Conclusions Among patients who use long-term bisphosphonates, the decision of switching to teriparatide should be made with caution, especially for patients at high risk of hip fracture.


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 99 (11) ◽  
pp. 4094-4100 ◽  
Author(s):  
Brian McNabb ◽  
Eric Vittinghoff ◽  
Richard Eastell ◽  
Ann V. Schwartz ◽  
Douglas C. Bauer ◽  
...  

Context: Women stopping alendronate are commonly monitored with serial bone mineral density (BMD) measurements, yet no information exists on how frequently or for whom these measurements should be performed. Objective: The objective of the study was to develop a tool to guide post-alendronate BMD monitoring. Design: A predictive model was constructed to estimate the time until a given percentage of women's BMD T-scores drop below a given threshold that indicates a management change (such as retreatment) would be considered. This model was then used to estimate the time it would take for groups of women defined by their baseline BMDs to drop below the given threshold. Setting: Data were derived from the Fracture Intervention Trial Long Term Extension (FLEX), the largest multicenter clinical trial of its type to date. Participants: Four hundred four women who had received an average of 5.1 years of alendronate during the Fracture Intervention Trial and were subsequently observed for 5 treatment-free years (on placebo) during the FLEX trial were used to estimate the change in BMD over time. Results: If a management change such as alendronate reinitiation would be considered when BMD T-score drops below −2.5, the model shows that women with total hip BMD greater than −1.9 T-scores at the time of alendronate discontinuation have less than a 20% probability that at follow-up, monitoring BMD will be below the threshold within 5 years. The model performed similarly, and results are provided over a range of management change thresholds from −1.75 to −3 T-scores. Conclusions: Using the tool developed in this analysis, it is possible to estimate when BMD repeat measurement after alendronate discontinuation could potentially be useful. Measuring BMD within 5 years after alendronate discontinuation is unlikely to change management for women with total hip BMD 0.6 T-scores above a prespecified retreatment threshold within the range of −1.75 to −3 T-scores.


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.


Author(s):  
Elizabeth Shane ◽  
Stephanie Shiau ◽  
Robert R Recker ◽  
Joan M Lappe ◽  
Sanchita Agarwal ◽  
...  

Abstract Context We have previously reported that teriparatide is associated with substantial increases in bone mineral density (BMD) at the lumbar spine (LS), total hip (TH) and femoral neck (FN) and small declines at the distal radius (DR) in 41 premenopausal women with idiopathic osteoporosis (IOP), all severely affected with low trauma fractures and/or very low BMD. Effects of teriparatide dissipate if not followed by antiresorptives. Objectives To assess the effects of 12 and 24 months (M) of denosumab in premenopausal women with IOP completing 24M of teriparatide. Design Preplanned phase 2B extension study Setting Tertiary referral centers Patients Premenopausal women with IOP Interventions Denosumab 60mg every 6 months for 12 and 24M Main Outcome Measures Within-group change in BMD at the LS at 12M. Secondary outcomes include change in 12M BMD at other sites, 24M BMD at all sites, trabecular bone score (TBS) and bone turnover markers (BTM). Findings After completing teriparatide, 32 participants took denosumab for 12M and 29 for 24M, with statistically significant increases in BMD at the LS (5.2±2.6% and 6.9±2.6%), TH (2.9±2.4% and 4.6±2.8%) and FN (3.0±3.8% and 4.7±4.9%). Over the entire 24M teriparatide and 24M denosumab treatment period, BMD increased by 21.9±7.8% at the LS, 9.8±4.6% at the TH and 9.5±4.7% at the FN (all p&lt;0.0001). TBS increased by 5.8±5.6% (p&lt;0.001). Serum BTM decreased by 75%-85% by 3M and remained suppressed through 12M of denosumab. Denosumab was generally well-tolerated. Conclusions These data support the use of sequential teriparatide and denosumab to increase BMD in premenopausal women with severe osteoporosis.


2007 ◽  
Vol 156 (1) ◽  
pp. 123-127 ◽  
Author(s):  
Tomasz Miazgowski ◽  
Slawomir Pynka ◽  
Marzena Noworyta-Ziętara ◽  
Barbara Krzyzanowska-Świniarska ◽  
Robert Pikul

Objective: The risk of non-vertebral fractures is increased in men with type 1 diabetes (DM1) but studies have shown only moderately decreased or normal bone mineral density (BMD) in these patients. No previous studies have evaluated hip strength and geometry indices in DM1 patients. This study was therefore designed to characterize associations between BMD, dual X-ray absorptiometry (DXA)-based hip strength indices, metabolic control, and DM1chronic complications. Design and methods: The study was performed on 36 males aged 43.6 ± 5.1 years with long-lasting DM1 and 36 healthy males matched for age, weight, and height. BMD in lumbar spine, total hip, upper and lower part of the femoral neck, hip axis length, cross-sectional area and moment of inertia (CSMI), and glycated hemoglobin (HbA1c) were measured. Results: DM1 men had decreased spine BMD (P < 0.05) and normal total hip BMD in comparison with controls. Hip geometry and strength indices were comparable in both groups. However, M1 men had decreased CSMI and upper femur BMD but these differences did not reach statistical significance (P = 0.06). BMD changes and hip strength parameters did not correlate with HbA1c. Conclusions: Middle-aged DM1 men have decreased lumbar spine BMD, normal hip BMD and normal hip strength indices. These changes are not influenced by metabolic control and presence of chronic microvascular complications.


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