Bone Turnover Markers and Treatment Efficacy in Postmenopausal Osteoporosis

Official title

Determination of Selective Bone Turnover Markers and Their Association With Treatment Efficacy in Primary Postmenopausal Osteoporotic Women: A Randomized Control Trial

Overview

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.

Detailed description

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.

Interventions

• Drug Alendronate, Ibandronate; Risedronate
  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.
• Drug Teriparatide
  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.

Primary outcome measures

• Change in Bone Turnover Markers (BTMs) [Time frame: Baseline, 3 months, and 6 months.]
• Change in Bone Mineral Density (BMD) [Time frame: Baseline and 6 months.]

Secondary outcome measures (1)

• Incidence of New Fractures [Time frame: Through study completion, an average of 6 months.]

Eligibility criteria

Inclusion criteria

• Postmenopausal women (at least one year since last menstrual cycle).
• Age greater than 50 years.
• Diagnosis of primary osteoporosis.
• Currently not on any anti-osteoporosis medications.
• Not taking Calcium or Vitamin D supplements.
• Volunteer to participate and provide informed consent.

Exclusion criteria

• Women with multiple vertebral fractures or severe lumbar degenerative changes.
• Use of hormone/estrogen therapy, calcitonin, oral bisphosphonates, IV ibandronate, IV Zoledronic acid, denosumab, or teriparatide within the past 18 months.
• Use of corticosteroids (short or long-term).
• History of hyperthyroidism, hypothyroidism, liver disease, kidney disease, or tumors.
• Presence of secondary causes of osteoporosis (e.g., eating disorders, celiac disease, diabetes, hematologic disorders).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Pakistan · 1 center

• Northwest General Hospital — Peshawar

Publications

• 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 T PMID 31440982
• 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. PMID 33382995
• 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. PMID 37204537
• 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. PMID 28455749
• 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. PMID 32887359
• 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. PMID 29623238
• 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. PMID 30449552
• 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. PMID 31419313

Identifiers

NCT: NCT07242612 · KMU/DIR/CTU/2025/008

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗