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This study investigates the use of blood tests known as Bone Turnover Markers (BTMs) to quickly monitor the effectiveness of osteoporosis treatment in postmenopausal women. Osteoporosis, which weakens bones and increases fracture risk, is typically monitored using a DEXA scan to measure bone density (BMD), but this method changes slowly. BTMs may show a response to medication within just 3 to 6 months. In this randomized controlled trial, 40 postmenopausal women with osteoporosis will be assigned to receive either antiresorptive drugs (which slow bone loss) or anabolic drugs (which build new bone), along with calcium and vitamin D. The study will compare how these treatments affect BTMs and BMD over six months to determine if BTMs can serve as an early and reliable indicator of treatment success, which could be particularly useful in regions like Pakistan where access to repeated DEXA scans is limited.
A randomized controlled trial will be conducted to evaluate the association between selective BTM and the efficacy of different drug therapies in primary postmenopausal osteoporotic women. The study is motivated by the high prevalence of osteoporosis in this demographic in Pakistan and the limitations of the current gold standard, BMD measured by DEXA scan, which reflects changes in bone strength at a delayed rate. BTMs, being biochemical indicators of bone formation and resorption, offer a dynamic and rapid assessment of bone metabolic activity, potentially providing an early measure of treatment response within months rather than years. The trial will enroll 40 eligible women over 50, who will be randomly and blindly assigned to one of two treatment groups: one receiving antiresorptive drugs (such as Alendronate) and the other receiving anabolic drugs (Teriparatide), both supplemented with calcium and vitamin D for a six-month period. The primary outcomes include the comparative change in specific BTMs (BsALP, TRACP-5b, and Sclerostin) at three and six months, and the change in BMD at six months. Secondary outcomes will assess the correlation between BTM and BMD changes, as well as fracture incidence and quality of life. By analyzing these parameters, the study aims to generate valuable evidence for the utility of BTMs in guiding and monitoring osteoporosis treatment in a Pakistani clinical setting, potentially leading to more responsive and personalized patient management.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Anabolic Therapy Group | Experimental | Participants in this group will receive the anabolic drug Teriparatide 20 mcg, administered as a daily subcutaneous injection, for a duration of 6 months. In addition, all participants in this arm will receive daily Calcium and Vitamin D supplements. |
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| Antiresorptive Therapy Group | Active Comparator | Participants will receive one of the following oral antiresorptive drugs for 6 months: Alendronate 70mg weekly, Ibandronate 150mg monthly, or Risedronate 150mg monthly. All participants will also receive Calcium and Vitamin D supplementation. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alendronate, Ibandronate; Risedronate | Drug | Oral bisphosphonate tablets. Participants will receive one of the following specific regimens: Alendronate 70mg taken once per week, Ibandronate 150mg taken once per month, or Risedronate 150mg taken once per month. This is combined with daily Calcium and Vitamin D supplementation. The total treatment duration is 6 months. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Bone Turnover Markers (BTMs) | Mean change from baseline in the serum levels of specific bone turnover markers, including the bone formation marker Bone-Specific Alkaline Phosphatase (BsALP) and the bone resorption marker Tartrate-Resistant Acid Phosphatase 5b (TRACP-5b), and the osteocyte marker Sclerostin. | Baseline, 3 months, and 6 months. |
| Change in Bone Mineral Density (BMD) | Mean change from baseline in Bone Mineral Density (BMD) T-score as measured by Dual-Energy X-ray Absorptiometry (DEXA) scans at the hip, spine, and femoral neck. | Baseline and 6 months. |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of New Fractures | The number of participants who experience any new fragility fractures during the study period. | Through study completion, an average of 6 months. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Asma Mehmood, PhDScholar | Contact | 0333-9400179 | asma13mehmood@gmail.com | |
| Rubina Nazli, PhD (Professor) | Contact | 0321-5773696 | rubinanazli44@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Asma Mehmood, PhD Scholar | Institute of Basic Medical Sciences, Khyber Medical University | Principal Investigator |
| Rubina Nazli, PhD | Institute of Basic Medical Sciences, Khyber Medical University | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Northwest General Hospital | Recruiting | Peshawar | Khyber Pakhtunkhwa | 25000 | Pakistan |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31440982 | Background | Lorentzon M, Branco J, Brandi ML, Bruyere O, Chapurlat R, Cooper C, Cortet B, Diez-Perez A, Ferrari S, Gasparik A, Herrmann M, Jorgensen NR, Kanis J, Kaufman JM, Laslop A, Locquet M, Matijevic R, McCloskey E, Minisola S, Pikner R, Reginster JY, Rizzoli R, Szulc P, Vlaskovska M, Cavalier E. Algorithm for the Use of Biochemical Markers of Bone Turnover in the Diagnosis, Assessment and Follow-Up of Treatment for Osteoporosis. Adv Ther. 2019 Oct;36(10):2811-2824. doi: 10.1007/s12325-019-01063-9. Epub 2019 Aug 22. | |
| 33382995 |
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A definitive plan for sharing individual participant data has not been established. The data collected, including de-identified individual participant records for primary and secondary outcomes, may be made available upon reasonable request after the primary results are published.
Data may become available beginning 6 months after the publication of the primary study findings and will be accessible for a period of 3 years.
Access to IPD will be considered for researchers who provide a methodologically sound proposal. Requests should be directed to the corresponding author. Approval will be subject to review by the study's supervisory committee and a signed data sharing agreement.
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| ID | Term |
|---|---|
| D010024 | Osteoporosis |
| D015663 | Osteoporosis, Postmenopausal |
| ID | Term |
|---|---|
| D001851 | Bone Diseases, Metabolic |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D008659 | Metabolic Diseases |
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| ID | Term |
|---|---|
| D019386 | Alendronate |
| D000077557 | Ibandronic Acid |
| D000068296 | Risedronic Acid |
| D019379 | Teriparatide |
| ID | Term |
|---|---|
| D004164 | Diphosphonates |
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
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Participants are randomly assigned to one of two parallel treatment groups to receive different drug interventions concurrently.
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The protocol states this will be a "double blinded study" where "the participant and researcher will be unaware of the interventions until the participants complete their 6 months of interventions. Only the research assistant will be aware of the interventions given."
|
|
| Teriparatide | Drug | A solution for subcutaneous injection. The dosage is 20 micrograms (mcg) injected once daily. This is combined with daily Calcium and Vitamin D supplementation. The total treatment duration is 6 months. |
|
|
| Arshad Hussain, M.D Consultant | Northwest General Hospital, Peshawar | Principal Investigator |
| Ehtesham Khan, PhD | InsInstitute of Basic Medical Sciences, Khyber Medical University | Principal Investigator |
| Background |
| Bhattoa HP, Cavalier E, Eastell R, Heijboer AC, Jorgensen NR, Makris K, Ulmer CZ, Kanis JA, Cooper C, Silverman SL, Vasikaran SD; IFCC-IOF Committee for Bone Metabolism. Analytical considerations and plans to standardize or harmonize assays for the reference bone turnover markers PINP and beta-CTX in blood. Clin Chim Acta. 2021 Apr;515:16-20. doi: 10.1016/j.cca.2020.12.023. Epub 2020 Dec 28. |
| 37204537 | Background | Nadeem S, Pervez A, Abid MA, Khalid RN, Rizvi NA, Aamdani SS, Ayub B, Mustafa MA, Ahmed S, Riaz M, Irfan K, Noordin S, Jafri L, Majid H, Umer M, Zehra N, Sheikh A, Haider AH, Khan AH. GRADE-ADOLOPMENT of clinical practice guideline for postmenopausal osteoporosis management-a Pakistani context. Arch Osteoporos. 2023 May 19;18(1):71. doi: 10.1007/s11657-023-01258-2. |
| 28455749 | Background | Jorgensen NR, Mollehave LT, Hansen YBL, Quardon N, Lylloff L, Linneberg A. Comparison of two automated assays of BTM (CTX and P1NP) and reference intervals in a Danish population. Osteoporos Int. 2017 Jul;28(7):2103-2113. doi: 10.1007/s00198-017-4026-z. Epub 2017 Apr 28. |
| 32887359 | Background | Moller AMJ, Delaisse JM, Olesen JB, Canto LM, Rogatto SR, Madsen JS, Soe K. Fusion Potential of Human Osteoclasts In Vitro Reflects Age, Menopause, and In Vivo Bone Resorption Levels of Their Donors-A Possible Involvement of DC-STAMP. Int J Mol Sci. 2020 Sep 2;21(17):6368. doi: 10.3390/ijms21176368. |
| 29623238 | Background | Patel D, Worley JR, Volgas DA, Crist BD. The Effectiveness of Osteoporosis Screening and Treatment in the Midwest. Geriatr Orthop Surg Rehabil. 2018 Mar 29;9:2151459318765844. doi: 10.1177/2151459318765844. eCollection 2018. |
| 30449552 | Background | Rizzoli R. Postmenopausal osteoporosis: Assessment and management. Best Pract Res Clin Endocrinol Metab. 2018 Oct;32(5):739-757. doi: 10.1016/j.beem.2018.09.005. Epub 2018 Sep 22. |
| 31419313 | Background | Cosman F, McMahon D, Dempster D, Nieves JW. Standard Versus Cyclic Teriparatide and Denosumab Treatment for Osteoporosis: A Randomized Trial. J Bone Miner Res. 2020 Feb;35(2):219-225. doi: 10.1002/jbmr.3850. Epub 2019 Oct 23. |
| D009750 |
| Nutritional and Metabolic Diseases |
| D011725 |
| Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D010281 | Parathyroid Hormone |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |