Effect of Vitamin D and Denosumab on Bone Remodelling in Women With Postmenopausal Osteoporosis

Menopause Clinical Trial

Official title:

Vitamin D Improves Osteoporosis in Postmenopausal Women With Denosumab Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05372224
• Other study ID #: 032.2020
• Status: Completed
• Phase: N/A
• Start date: June 22, 2020
• Est. completion date: June 22, 2021

Study information

• Verified date: February 2023
• Source: Hospital Regional 1o de Octubre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Denosumab is a monoclonal antibody against RANKL ligand, which is used as an alternative treatment for osteoporosis in patients who have a poor response to first-line antiresorptive therapy. However, discontinuation of denosumab produces a rapid increase in bone turnover, bone loss and potentially increased risk of multiple vertebral fractures.

Description:

76 postmenopausal women from the climacteric clinic of the regional hospital "1o de Octubre" of the Institute of Security and Social Services for State Workers (ISSSTE) were firstly considered, of which 23 presented elimination criteria and only 55 who had received denosumab therapy for an average of 2.5 years without a significant improvement in hip and lumbar spine T-scores were enrolled. First, a general medical evaluation was performed. Serum levels of vitamin D were analysed to find the prevalence of hypovitaminosis D. A bone mineral density test was done to calculate hip and lumbar spine T-scores. Then, vitamin D was administrated daily for one year at a dose of 4,000 IU and the studies were repeated after one year. Statistical analysis was performed using PAST 3.0 and GraphPad Prism 8.4.3. software. The arithmetic median (µ) and standard deviation (S.D.) were calculated using Excel-Word. Graphics were constructed with GraphPad Prism 8.4.3 and tables with Excel Word. Categorical variables were analysed with chi-squared or Fisher exact test depending on the number of participants in each cell. Normality was determined using the Shapiro-Wilk test. To compare two paired samples, the Wilcoxon signed-rank test was utilized. The assigned α value for this study was <0.05. In all cases, if a Montecarlo permutation was available, the exact p-value was taken instead of the raw p-value.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: June 22, 2021
• Est. primary completion date: June 22, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 45 Years to 89 Years

Eligibility

Inclusion Criteria:

• Diagnosis of postmenopausal osteoporosis or osteopenia in treatment with denosumab 60mg every six months plus calcium carbonate 1.2g/day + vitamin D 800IU/day.
• Diagnosis of hypovitaminosis D, with serum cholecalciferol values <30ng/dL.

Exclusion Criteria:

• Incomplete clinical records or clinical records.
• Age over 90 years.
• Diagnosis of secondary (hereditary) osteoporosis.
• History of prolonged use of steroids.
• Lack of adherence to medical treatment.
• Diagnosis of cancer.
• Diagnosis of depression.
• Diagnosis of Celiac disease or with the presence of alterations in intestinal absorption.
• Allergies to any of the medications administered.

Related Conditions & MeSH terms

• Avitaminosis
• Hypovitaminosis D
• Menopause
• Osteoporosis
• Osteoporosis, Postmenopausal
• Rickets
• Vitamin D Deficiency

Intervention

Drug:
• Cholecalciferol
4000 IU were administrated once a day for 3 months.

Locations

Country	Name	City	State
Mexico	Patricia Loranca-Moreno	Mexico City	Gustavo A. Madero

Sponsors (3)

Lead Sponsor	Collaborator
Hospital Regional 1o de Octubre	National Polytechnic Institute, Mexico, Universidad Nacional Autonoma de Mexico

Country where clinical trial is conducted

Mexico, 

References & Publications (7)

Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C; FREEDOM Trial. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009 Aug 20;361(8):756-65. doi: 10.1056/NEJMoa0809493. Epub 2009 Aug 11. Erratum In: N Engl J Med. 2009 Nov 5;361(19):1914. — View Citation

Kanis JA, Cooper C, Rizzoli R, Reginster JY; Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis (ESCEO) and the Committees of Scientific Advisors and National Societies of the International Osteoporosis Foundation (IOF). European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int. 2019 Jan;30(1):3-44. doi: 10.1007/s00198-018-4704-5. Epub 2018 Oct 15. Erratum In: Osteoporos Int. 2020 Jan;31(1):209. Osteoporos Int. 2020 Apr;31(4):801. — View Citation

McClung MR, Wagman RB, Miller PD, Wang A, Lewiecki EM. Observations following discontinuation of long-term denosumab therapy. Osteoporos Int. 2017 May;28(5):1723-1732. doi: 10.1007/s00198-017-3919-1. Epub 2017 Jan 31. — View Citation

Miyoshi A, Kameda H, Nagai S, Nakamura A, Miya A, Takase T, Atsumi T, Miyoshi H. Beneficial effects of switching to denosumab from bisphosphonates or selective estrogen receptor modulators in postmenopausal women with type 2 diabetes and osteopenia/osteoporosis. J Diabetes Investig. 2021 Jul;12(7):1293-1300. doi: 10.1111/jdi.13458. Epub 2020 Dec 13. — View Citation

Saag KG, Petersen J, Brandi ML, Karaplis AC, Lorentzon M, Thomas T, Maddox J, Fan M, Meisner PD, Grauer A. Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis. N Engl J Med. 2017 Oct 12;377(15):1417-1427. doi: 10.1056/NEJMoa1708322. Epub 2017 Sep 11. — View Citation

Takeuchi T, Tanaka Y, Soen S, Yamanaka H, Yoneda T, Tanaka S, Nitta T, Okubo N, Genant HK, van der Heijde D. Effects of the anti-RANKL antibody denosumab on joint structural damage in patients with rheumatoid arthritis treated with conventional synthetic disease-modifying antirheumatic drugs (DESIRABLE study): a randomised, double-blind, placebo-controlled phase 3 trial. Ann Rheum Dis. 2019 Jul;78(7):899-907. doi: 10.1136/annrheumdis-2018-214827. Epub 2019 Apr 29. — View Citation

Tsourdi E, Langdahl B, Cohen-Solal M, Aubry-Rozier B, Eriksen EF, Guanabens N, Obermayer-Pietsch B, Ralston SH, Eastell R, Zillikens MC. Discontinuation of Denosumab therapy for osteoporosis: A systematic review and position statement by ECTS. Bone. 2017 Dec;105:11-17. doi: 10.1016/j.bone.2017.08.003. Epub 2017 Aug 5. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with hip T-score improvement at 12 months	It refers to the number of participants who improved their hip T-score at three months after treatment.	12 months
Primary	Number of participants with lumbar spine T-score improvement at 12 months	It refers to the number of participants who improved their lumbar spine T-score at three months after treatment.	12 months
Primary	Number of participants with osteoporosis of the hip at 12 months	It refers to the number of participants that present a hip T-score above -2.5 three months after treatment.	12 months
Primary	Number of participants with osteoporosis of the lumbar spine at 12 months	It refers to the number of participants that present a lumbar spine T-score greater than -2.5 three months after treatment.	12 months
Primary	Number of participants with osteopenia on the hip at 12 months	It refers to the number of participants that present a hip T-score from -1 to -2.4 three months after treatment.	12 months
Primary	Number of participants with osteopenia of the lumbar spine at 12 months	It refers to the number of participants that present a lumbar spine T-score from -1 to -2.4 three months after treatment.	12 months
Primary	Number of participants with normal hip T-score at 12 months	It refers to the number of participants that present a hip T-score below -1 three months after treatment.	12 months
Primary	Number of participants with normal lumbar spine T-score at 12 months	It refers to the number of participants that present a lumbar spine T-score below -1 three months after treatment.	12 months
Primary	Number of participants with improvement in serum levels of vitamin D at 12 months	Improvement in serum levels of 25-hydroxy vitamin D [25(OH)D] was considered when serum vitamin D levels increased concerning baseline levels.	12 months
Primary	Number of participants with clinical remission of hypovitaminosis D at 12 months	Remission of hypovitaminosis D was considered when serum levels of 25-hydroxy vitamin D [25(OH)D] were above 29 pg/ml.	12 months
Secondary	Number of participants with vitamin D sufficiency at 12 months	It refers to the number of participants who reached serum levels of vitamin D above 29 pg/ml after three months of treatment.	12 months
Secondary	Number of participants with vitamin D insufficiency at 12 months	It refers to the number of participants who reached serum levels of vitamin D of 21 to 29 pg/ml after three months of treatment.	12 months
Secondary	Number of participants with vitamin D deficiency at 12 months	It refers to the number of participants who reached serum levels of vitamin D less than 20 pg/ml after three months of treatment.	12 months