Therapeutic Prospects of HMG-CoA Reductase Inhibitors, Atorvastatin and Rosuvastatin, in Osteoporotic Patients (statins on BMD)

Osteoporosis is one of the most common chronic skeletal disorders, particularly among postmenopausal women, and is associated with an increased risk of fragility fractures, disability, and reduced quality of life. Several preclinical studies and retrospective clinical studies have suggested that statins may exert beneficial effects on bone metabolism by promoting bone formation and reducing bone resorption. Since osteoporosis and hyperlipidemia frequently coexist in postmenopausal women, the concomitant use of statins with standard osteoporosis therapy may provide dual clinical benefits by improving both skeletal and cardiovascular outcomes. In this prospective interventional study, atorvastatin and Rosuvastatin was administered according to current clinical practice guidelines only to participants with an indication for statin therapy, defined as an atherosclerotic cardiovascular disease (ASCVD) risk score of ≥5%. The effects of standard osteoporosis therapy alone (alendronate, calcium, and vitamin D) were compared with those of standard therapy plus atorvastatin and compared with those of standard therapy plus rosuvastatin. The study aims to evaluate the effect of adjunctive statin therapy on bone mineral density and biochemical markers of bone turnover, including markers of bone formation and bone resorption, in postmenopausal women with osteoporosis.

Study Overview

• Status: Completed
• Conditions: Osteoporosis, Postmenopausal; Statin Therapy
• Intervention / Treatment: Drug: Alendronate 70 mg tablets; Drug: Atorvastatin; Drug: Rosuvastatin

Detailed Description

Osteoporosis is a major public health problem, particularly among postmenopausal women, and is characterized by reduced bone mineral density (BMD) and deterioration of bone microarchitecture, leading to an increased risk of fragility fractures. Hyperlipidemia frequently coexists with osteoporosis in this population because both conditions share several risk factors, including aging and menopause. Experimental studies and retrospective clinical studies have suggested that statins may exert favorable effects on bone metabolism by enhancing osteoblast activity, suppressing osteoclast-mediated bone resorption, and promoting bone formation. These findings raise the possibility that statins may provide additional skeletal benefits when administered in combination with standard anti-osteoporotic therapy.

The present prospective interventional study was designed to evaluate the effect of adjunctive statin therapy on bone health in postmenopausal women with osteoporosis. In addition to assessing the overall effect of statins, the study aimed to compare the skeletal effects of two statins with different physicochemical properties: atorvastatin, a lipophilic statin, and rosuvastatin, a hydrophilic statin. The study also investigated whether combining statins with standard osteoporosis therapy provides greater improvement in bone mineral density and bone turnover markers than standard osteoporosis therapy alone. Furthermore, the study evaluated the relationship between changes in lipid profile parameters and improvements in bone mineral density in order to determine whether lipid lowering is associated with skeletal response.

The study protocol was reviewed and approved by the Ethics Committee of the College of Medicine, University of Kufa, and the required administrative and regulatory approvals were obtained from the Iraqi Ministry of Health through the Najaf Health Directorate before study initiation. All participants were informed about study objectives, procedures, potential benefits and possible risks before study initiation. All therapeutic interventions were performed in accordance with current clinical practice guidelines. Statin therapy was prescribed only for participants with a guideline-based clinical indication for treatment (ASCVD risk ≥5%), and no participant received statin therapy solely for research purposes.

Participants were allocated into three study groups according to their estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk and clinical indication for statin therapy. Women with an ASCVD risk of less than 5%, who had no guideline-based indication for statin treatment, received standard osteoporosis therapy consisting of alendronate, calcium, and vitamin D. Women with an ASCVD risk of 5% or greater, for whom statin therapy was clinically indicated according to current treatment guidelines, received standard osteoporosis therapy plus statin treatment. Participants in this category were randomly assigned to receive either atorvastatin or rosuvastatin in addition to alendronate, calcium, and vitamin D.

Eligible participants were postmenopausal women diagnosed with osteoporosis, defined by a lumbar spine T-score of -2.5 or lower on dual-energy X-ray absorptiometry (DXA). Before treatment initiation, all participants underwent baseline clinical assessment, DXA measurement of bone mineral density, and blood sample collection. Laboratory investigations included lipid profile (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides), serum calcium, vitamin D, osteocalcin, bone-specific alkaline phosphatase (BALP), C-terminal telopeptide of type I collagen (CTX-1), and bone sialoprotein (BSP).

Participants were followed for six months, during which treatment adherence was monitored. At the end of the follow-up period, DXA measurements and laboratory investigations were repeated using the same assessment methods. Changes in bone mineral density, bone turnover markers, calcium, vitamin D, and lipid profile were compared within each treatment group and between groups. The primary objective was to determine whether the addition of statin therapy to standard osteoporosis treatment resulted in greater improvement in bone mineral density than standard therapy alone. Secondary objectives included comparing the skeletal effects of lipophilic and hydrophilic statins and evaluating the association between improvements in lipid profile and changes in bone mineral density and biochemical markers of bone turnover.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Iraq
  • Najaf, Iraq
    • AL-KUFA UNIVERSITY/College of Pharmacy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• patients aged ≥ 55 diagnosed with primary age-related osteoporosis according to European guidance osteoporosis, T-score ≤-2.5, and did not receive any treatment for osteoporosis previously or statins.

Exclusion Criteria:

• patients who had been taking antiresorptive, bone forming or statins, patients who were taking any medications that can affect osteoporosis. Patients who had medical issues that could be a secondary cause for osteoporosis. and patients who were allergic to alendronate or statins were excluded from the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: standard osteoporosis therapay; Participants with a 10-year Atherosclerotic Cardiovascular Disease (ASCVD) risk <5% and osteoporosis (T-score ≤ -2.5) received standard osteoporosis therapy consisting of alendronate, calcium, and vitamin D.	Drug: Alendronate 70 mg tablets; Before treatment initiation, all participants underwent baseline evaluation, including dual-energy X-ray absorptiometry (DXA) for bone mineral density assessment, measurement of blood pressure, fasting blood glucose, and lipid profile, as well as collection of demographic and clinical data. Blood samples were obtained from all participants, and serum was separated for the assessment of biochemical markers of bone metabolism, including osteocalcin, bone-specific alkaline phosphatase (BALP), C-terminal telopeptide of type I collagen (CTX-1), bone sialoprotein (BSP), serum calcium, and vitamin D concentrations. Participants diagnosed with osteoporosis received standard osteoporosis therapy consisting of alendronate 70 mg administered once weekly, together with calcium carbonate and vitamin D supplementation. Calcium and vitamin D doses were individualized according to each participant's clinical requirements and baseline laboratory findings, in accordance with standard clinical practice.
Experimental: Atorvastatin Plus Standard osteoporosis therapy; Participants with a 10-year ASCVD risk ≥5% and osteoporosis received atorvastatin in addition to standard osteoporosis therapy (alendronate, calcium, and vitamin D).	Drug: Alendronate 70 mg tablets; Before treatment initiation, all participants underwent baseline evaluation, including dual-energy X-ray absorptiometry (DXA) for bone mineral density assessment, measurement of blood pressure, fasting blood glucose, and lipid profile, as well as collection of demographic and clinical data. Blood samples were obtained from all participants, and serum was separated for the assessment of biochemical markers of bone metabolism, including osteocalcin, bone-specific alkaline phosphatase (BALP), C-terminal telopeptide of type I collagen (CTX-1), bone sialoprotein (BSP), serum calcium, and vitamin D concentrations. Participants diagnosed with osteoporosis received standard osteoporosis therapy consisting of alendronate 70 mg administered once weekly, together with calcium carbonate and vitamin D supplementation. Calcium and vitamin D doses were individualized according to each participant's clinical requirements and baseline laboratory findings, in accordance with standard clinical practice.; Drug: Atorvastatin; Participants diagnosed with osteoporosis and having an estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk of ≥5%, indicating guideline-based statin therapy, received atorvastatin in addition to standard osteoporosis therapy consisting of alendronate 70 mg administered once weekly, calcium carbonate, and vitamin D supplementation. Atorvastatin was administered once daily at a dose of 20-40 mg, individualized according to each participant's cardiovascular risk assessment and baseline lipid profile, in accordance with current clinical practice guidelines. Calcium and vitamin D doses were also individualized according to each participant's clinical requirements and baseline laboratory findings. Before treatment initiation, all participants underwent baseline evaluation, including dual-energy X-ray absorptiometry (DXA), blood pressure measurement, fasting blood glucose, lipid profile assessment, collection of demographic and clinical data, and blood sampling for serum ana
Experimental: rosuvastatin plus standard osteoporosis therapy; Participants with a 10-year ASCVD risk ≥5% and osteoporosis received rosuvastatin in addition to standard osteoporosis therapy (alendronate, calcium, and vitamin D).	Drug: Alendronate 70 mg tablets; Before treatment initiation, all participants underwent baseline evaluation, including dual-energy X-ray absorptiometry (DXA) for bone mineral density assessment, measurement of blood pressure, fasting blood glucose, and lipid profile, as well as collection of demographic and clinical data. Blood samples were obtained from all participants, and serum was separated for the assessment of biochemical markers of bone metabolism, including osteocalcin, bone-specific alkaline phosphatase (BALP), C-terminal telopeptide of type I collagen (CTX-1), bone sialoprotein (BSP), serum calcium, and vitamin D concentrations. Participants diagnosed with osteoporosis received standard osteoporosis therapy consisting of alendronate 70 mg administered once weekly, together with calcium carbonate and vitamin D supplementation. Calcium and vitamin D doses were individualized according to each participant's clinical requirements and baseline laboratory findings, in accordance with standard clinical practice.; Drug: Rosuvastatin; Participants diagnosed with osteoporosis and having an estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk of ≥5%, indicating guideline-based statin therapy, received rosuvastatin in addition to standard osteoporosis therapy consisting of alendronate 70 mg administered once weekly, calcium carbonate, and vitamin D supplementation. Rosuvastatin was administered once daily at a dose of 10-40 mg, individualized according to each participant's cardiovascular risk assessment and baseline lipid profile, in accordance with current clinical practice guidelines. Calcium and vitamin D doses were also individualized according to each participant's clinical requirements and baseline laboratory findings. Before treatment initiation, all participants underwent baseline evaluation, including dual-energy X-ray absorptiometry (DXA), blood pressure measurement, fasting blood glucose, lipid profile assessment, collection of demographic and clinical data, and blood sampling for serum ana

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in bone mineral density (lumbar spine and hip)	Bone mineral density (BMD) was assessed at baseline and after 6 months using dual-energy X-ray absorptiometry (DXA). Measurements were obtained at the lumbar spine and left hip, and corresponding T-scores were recorded to evaluate changes in bone density following treatment.	base line and after 6 months
change in serum calcium and vitamin D levels	Blood samples were collected from all participants at baseline and after 6 months of treatment. Serum calcium and vitamin D levels were measured to evaluate changes in bone mineral metabolism following treatment.	baseline and 6 months
Change in Serum Bone turnover biomarkers	Change in serum concentrations of osteocalcin, bone-specific alkaline phosphatase (BSAP), C-terminal telopeptide of type I collagen (CTX-I), and bone sialoprotein (BSP) from baseline to 6 months as indicators of bone formation and bone resorption.	Baseline and after 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum lipid profile	Change in serum concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides from baseline to 6 months.	baseline and 6 months

Collaborators and Investigators

• Sponsor: Alkufa university\\collage of pharmacy

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2025
• Primary Completion (Actual): July 1, 2026
• Study Completion (Actual): July 1, 2026

Study Registration Dates

• First Submitted: July 16, 2026
• First Submitted That Met QC Criteria: July 16, 2026
• First Posted (Actual): July 21, 2026

Study Record Updates

• Last Update Posted (Actual): July 21, 2026
• Last Update Submitted That Met QC Criteria: July 16, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Postmenopausal osteoporosis; statin; alendronate; bone mineral density; bone turnover markers.
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Bone Diseases, Metabolic; Osteoporosis; Nutritional and Metabolic Diseases; Osteoporosis, Postmenopausal; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fatty Acids; Lipids; Azoles; Hydrocarbons; Amides; Pyrimidines; Hydrocarbons, Halogenated; Organophosphorus Compounds; Pyrroles; Heptanoic Acids; Organophosphonates; Sulfonamides; Sulfones; Fluorobenzenes; Hydrocarbons, Fluorinated; Diphosphonates; Atorvastatin; Rosuvastatin Calcium; Alendronate
• Other Study ID Numbers: KU-OP-2025-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared because of participant confidentiality and institutional restrictions on data sharing.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No