Clinical trial NCT05346419: Antiresorptive Effect of Treatment With Risedronate and Vitamin D in Postmenopausal Patients
Official title: Risedronate With High-dose Vitamin D Resolves Hyperparathyroidism and Hypovitaminosis D But Not Osteoporosis in Mexican Postmenopausal Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Postmenopausal Osteoporosis
Hypovitaminosis D
Hyperparathyroidism
Keywords: Postmenopause
Postmenopausal Osteoporosis
Hypovitaminosis D
Hyperparathyroidism
Risedronate
Osteopenia
Bone Mineral Density
Bone resorption
Lead sponsor: Hospital Regional 1o de Octubre
Sponsor class: OTHER
Collaborators: name: National Polytechnic Institute, Mexico
name: Universidad Nacional Autonoma de Mexico
First posted: 2022-04-26
Enrollment: 33
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 78
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 33 participants between 40 and 78 years old with a diagnosis of postmenopausal osteoporosis or osteopenia with associated hyperparathyroidism, hypovitaminosis or both conditions were selected. All participants were treated for 6 months with risedronate 35 mg and vitamin D 2800 IU once a week, with additional daily vitamin D supplementation of 4000 IU.
Primary purpose: TREATMENT

Brief summary: Osteoporosis is defined as a systemic disease of bone mineralization, characterized by a decrease in bone mineral density that causes bone fragility and increases the risk of fractures during menopause. Recently, a high prevalence of hypovitaminosis D has been found worldwide, which could trigger a state of secondary hyperparathyroidism that can worsen the state of postmenopausal patients with osteoporosis. An open-label, clinical trial was conducted in Mexican women with postmenopausal osteopenia-osteoporosis to determine the efficacy of the combined treatment with risedronate and high-dose vitamin D in improving bone mineral density, hyperparathyroidism, and hypovitaminosis D.

Detailed description: Participants were selected from the climacteric clinic of the regional hospital "1ro de Octubre-Instituto de Seguridad y Servicios Sociales para Los Trabajadores del Estado (ISSSTE)", Mexico. All participants voluntarily accepted to be part of the study and provided written informed consent.This study was approved by the institutional ethical committee of the hospital with registration number COFEPRIS 17 CI 09005135 with the internal registration number 118.2021. Every participant was clinically examined. Their metabolic state was assessed by considering height, weight, body mass index (BMI) and the percentage of Hb1Ac.

33 patients were included among 40 to 78 years with the diagnosis of postmenopausal osteoporosis with associated hyperparathyroidism, hypovitaminosis D or both conditions. All the patients were treated for 6 months with 35 mg of risedronate and 2800 IU of vitamin D once a week, with additional daily supplementation of 4000 IU of vitamin D.

Statical analysis was performed using PAST 3.0 and GraphPad Prism 8.4.3. software. Some statical parameters, such as arithmetic median (µ), and standard deviation (S.D.) were calculated using Excel-Word. Graphics were constructed with GraphPad Prism 8.4.3 and tables were done in Excel-Word. The assigned α value for this study was \<0.05.

Eligibility criteria: Inclusion Criteria:

* Participants with a diagnosis of postmenopausal osteoporosis or osteopenia.
* Participants with a diagnosis of hyperparathyroidism or hypovitaminosis D.
* Participants who accepted to participate and that provided informed consent.

Exclusion Criteria:

* Participants with oncological pathologies.
* Participants with recent fractures.
* Participants with gastric intolerance or hypersensitivity to the drugs.
* Participants were under treatment with another antiresorptive or bone-forming drug, or if they were receiving treatment with thiazide diuretics, lithium, teriparatide or glucocorticoids.
* Participants with Addison's disease, pheochromocytoma or depressive disorders.

Primary outcomes:
measure: Remission of hyperparathyroidism
timeFrame: 6 months
measure: Remission of hypovitaminosis D
timeFrame: 6 months
measure: Remission of osteopenia
timeFrame: 6 months
measure: Remission of Osteoporosis
timeFrame: 6 months
Secondary outcomes:
measure: Change from baseline serum calcium at 6 months
timeFrame: 6 months
measure: Change from baseline serum phosphorus at 6 months
timeFrame: 6 months
measure: Change from baseline urinary calcium at 6 months
timeFrame: 6 months
measure: Change from bone resorption biomarker at 6 months
timeFrame: 6 months
measure: Fracture Risk Assessment Tool (FRAX®) for hip fracture
timeFrame: 6 months
measure: Fracture Risk Assessment Tool for major osteoporotic fracture (FRAX® Mo)
timeFrame: 6 months
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: Peri-postmenopause and bone metabolism clinic. Regional Hospital October 1st ISSSTE
Study officials:
affiliation: Tissue Bioengineering Laboratory, National Autonomous University of Mexico [UNAM]
name: Juan M Ocampo Godínez, M.D., Ph.D.
role: STUDY_DIRECTOR
affiliation: Peri-postmenopause and bone metabolism clinic. Regional Hospital October 1st ISSSTE.
name: Patricia Loranca-Moreno, M.D., M.Sc.
role: STUDY_DIRECTOR
affiliation: Peri-postmenopause and bone metabolism clinic. Regional Hospital October 1st ISSSTE
name: Merle Y Hernández-Castañón, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cossio-Bolanos M, Vidal-Espinoza R, Fuentes-Lopez J, Castelli Correia de Campos LF, Andruske CL, Urra-Albornoz C, Alvear Vasquez F, Gomez-Campos R. Reference values for bone density and bone mineral content from 5 to 80 years old in a province of Chile. PeerJ. 2022 Mar 23;10:e13092. doi: 10.7717/peerj.13092. eCollection 2022.
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.
citation: Deng W, Han JC, Chen L, Qi WL. Estrogen receptor alpha gene PvuII polymorphism and risk of fracture in postmenopausal women: a meta-analysis. Genet Mol Res. 2015 Feb 13;14(1):1293-300. doi: 10.4238/2015.February.13.8.
citation: Aziziyeh R, Amin M, Habib M, Perlaza JG, McTavish RK, Ludke A, Fernandes S, Sripada K, Cameron C. A scorecard for osteoporosis in four Latin American countries: Brazil, Mexico, Colombia, and Argentina. Arch Osteoporos. 2019 Jun 27;14(1):69. doi: 10.1007/s11657-019-0622-1.
citation: Moschonis G, van den Heuvel EG, Mavrogianni C, Manios Y. Effect of Vitamin D-Enriched Gouda-Type Cheese Consumption on Biochemical Markers of Bone Metabolism in Postmenopausal Women in Greece. Nutrients. 2021 Aug 27;13(9):2985. doi: 10.3390/nu13092985.
citation: Bouloukaki I, Markakis M, Pateli R, Lyronis I, Schiza S, Tsiligianni I. Vitamin D levels in primary care patients: correlations with clinical, seasonal, and quality-of-life parameters. Fam Pract. 2022 Jul 19;39(4):678-684. doi: 10.1093/fampra/cmac012.
citation: Dixit V, Tripathi RL, Dhanwal DK. Lack of secondary hyperparathyroidism in sub-group of vitamin D deficient postmenopausal women: Is VDR gene polymorphism behind this mystery? Diabetes Metab Syndr. 2022 Jan;16(1):102381. doi: 10.1016/j.dsx.2021.102381. Epub 2021 Dec 28.
citation: Lips P, Hosking D, Lippuner K, Norquist JM, Wehren L, Maalouf G, Ragi-Eis S, Chandler J. The prevalence of vitamin D inadequacy amongst women with osteoporosis: an international epidemiological investigation. J Intern Med. 2006 Sep;260(3):245-54. doi: 10.1111/j.1365-2796.2006.01685.x.
citation: Martinez-Zavala N, Lopez-Sanchez GN, Vergara-Lopez A, Chavez-Tapia NC, Uribe M, Nuno-Lambarri N. Vitamin D deficiency in Mexicans have a high prevalence: a cross-sectional analysis of the patients from the Centro Medico Nacional 20 de Noviembre. Arch Osteoporos. 2020 Jun 16;15(1):88. doi: 10.1007/s11657-020-00765-w.
citation: Wihlborg A, Bergstrom K, Gerdhem P, Bergstrom I. Parathyroid Hormone Disturbances in Postmenopausal Women with Distal Forearm Fracture. World J Surg. 2022 Jan;46(1):128-135. doi: 10.1007/s00268-021-06331-w. Epub 2021 Oct 13.
citation: Yalla N, Bobba G, Guo G, Stankiewicz A, Ostlund R. Parathyroid hormone reference ranges in healthy individuals classified by vitamin D status. J Endocrinol Invest. 2019 Nov;42(11):1353-1360. doi: 10.1007/s40618-019-01075-w. Epub 2019 Jul 4.
citation: Clark P, Vivanco-Munoz N, Pina JT, Rivas-Ruiz R, Huitron G, Chico-Barba G, Reza-Albarran AA. High prevalence of hypovitaminosis D in Mexicans aged 14 years and older and its correlation with parathyroid hormone. Arch Osteoporos. 2015;10:225. doi: 10.1007/s11657-015-0225-4. Epub 2015 Jul 14.
citation: Yuan F, Peng W, Yang C, Zheng J. Teriparatide versus bisphosphonates for treatment of postmenopausal osteoporosis: A meta-analysis. Int J Surg. 2019 Jun;66:1-11. doi: 10.1016/j.ijsu.2019.03.004. Epub 2019 Mar 16.
citation: Miller PD, Hattersley G, Riis BJ, Williams GC, Lau E, Russo LA, Alexandersen P, Zerbini CA, Hu MY, Harris AG, Fitzpatrick LA, Cosman F, Christiansen C; ACTIVE Study Investigators. Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial. JAMA. 2016 Aug 16;316(7):722-33. doi: 10.1001/jama.2016.11136.
citation: Soreskog E, Lindberg I, Kanis JA, Akesson KE, Willems D, Lorentzon M, Strom O, Berling P, Borgstrom F. Cost-effectiveness of romosozumab for the treatment of postmenopausal women with severe osteoporosis at high risk of fracture in Sweden. Osteoporos Int. 2021 Mar;32(3):585-594. doi: 10.1007/s00198-020-05780-8. Epub 2021 Jan 6.
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.
citation: Eastell R, Rosen CJ, Black DM, Cheung AM, Murad MH, Shoback D. Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society* Clinical Practice Guideline. J Clin Endocrinol Metab. 2019 May 1;104(5):1595-1622. doi: 10.1210/jc.2019-00221.
citation: Kobayakawa T, Miyazaki A, Saito M, Suzuki T, Takahashi J, Nakamura Y. Denosumab versus romosozumab for postmenopausal osteoporosis treatment. Sci Rep. 2021 Jun 3;11(1):11801. doi: 10.1038/s41598-021-91248-6.
citation: Hiligsmann M, Reginster JY. Cost-effectiveness of gastro-resistant risedronate tablets for the treatment of postmenopausal women with osteoporosis in France. Osteoporos Int. 2019 Mar;30(3):649-658. doi: 10.1007/s00198-018-04821-7. Epub 2019 Jan 30.
citation: McClung MR, Ebetino FH. History of risedronate. Bone. 2020 Aug;137:115407. doi: 10.1016/j.bone.2020.115407. Epub 2020 May 6.
citation: American Geriatrics Society Workgroup on Vitamin D Supplementation for Older Adults. Recommendations abstracted from the American Geriatrics Society Consensus Statement on vitamin D for Prevention of Falls and Their Consequences. J Am Geriatr Soc. 2014 Jan;62(1):147-52. doi: 10.1111/jgs.12631. Epub 2013 Dec 18.
citation: Jilka RL, Weinstein RS, Bellido T, Roberson P, Parfitt AM, Manolagas SC. Increased bone formation by prevention of osteoblast apoptosis with parathyroid hormone. J Clin Invest. 1999 Aug;104(4):439-46. doi: 10.1172/JCI6610.
citation: Balani DH, Ono N, Kronenberg HM. Parathyroid hormone regulates fates of murine osteoblast precursors in vivo. J Clin Invest. 2017 Sep 1;127(9):3327-3338. doi: 10.1172/JCI91699. Epub 2017 Jul 31.
citation: Brent MB, Stoltenborg FE, Bruel A, Thomsen JS. Teriparatide and Abaloparatide Have a Similar Effect on Bone in Mice. Front Endocrinol (Lausanne). 2021 Apr 19;12:628994. doi: 10.3389/fendo.2021.628994. eCollection 2021.
citation: McClung MR, Harvey NC, Fitzpatrick LA, Miller PD, Hattersley G, Wang Y, Cosman F. Effects of abaloparatide on bone mineral density and risk of fracture in postmenopausal women aged 80 years or older with osteoporosis. Menopause. 2018 Jul;25(7):767-771. doi: 10.1097/GME.0000000000001080.
citation: Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001 May 10;344(19):1434-41. doi: 10.1056/NEJM200105103441904.
citation: Haas AV, LeBoff MS. Osteoanabolic Agents for Osteoporosis. J Endocr Soc. 2018 Jul 9;2(8):922-932. doi: 10.1210/js.2018-00118. eCollection 2018 Aug 1.
citation: Lindsay R, Nieves J, Formica C, Henneman E, Woelfert L, Shen V, Dempster D, Cosman F. Randomised controlled study of effect of parathyroid hormone on vertebral-bone mass and fracture incidence among postmenopausal women on oestrogen with osteoporosis. Lancet. 1997 Aug 23;350(9077):550-5. doi: 10.1016/S0140-6736(97)02342-8.
citation: Choi H, Magyar CE, Nervina JM, Tetradis S. Different duration of parathyroid hormone exposure distinctively regulates primary response genes Nurr1 and RANKL in osteoblasts. PLoS One. 2018 Dec 21;13(12):e0208514. doi: 10.1371/journal.pone.0208514. eCollection 2018.
citation: Choudhary S, Santone E, Yee SP, Lorenzo J, Adams DJ, Goetjen A, McCarthy MB, Mazzocca AD, Pilbeam C. Continuous PTH in Male Mice Causes Bone Loss Because It Induces Serum Amyloid A. Endocrinology. 2018 Jul 1;159(7):2759-2776. doi: 10.1210/en.2018-00265.
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.