Comparison of the pleiotropic effect of atorvastatin and rosuvastatin on postmenopausal changes in bone turnover: A randomized comparative study

Abstract

Background:

Statins are the first-line treatment for dyslipidemia, which is a major modifiable risk factor for atherosclerotic cardiovascular disease. Studies have shown that in addition to the beneficial lipid-lowering effect, statins also exhibit a number of pleiotropic effects that may find application in other diseases, including osteoporosis. This study aimed to assess the effect of statins on bone turnover, as measured by the concentration of bone turnover markers, and to compare the effect of atorvastatin as a lipophilic statin and rosuvastatin as a hydrophilic statin.

Methods:

This study included 34 postmenopausal women aged < 65 years with newly diagnosed dyslipidemia requiring statin therapy. Patients were randomly assigned to receive a statin drug. Statins were initiated at standard doses of 5 to 10 mg of rosuvastatin and 20 mg of atorvastatin. The levels of C-terminal telopeptide of type I collagen as a bone resorption marker and N-terminal propeptide of procollagen type I as a marker of bone formation, lipid concentrations and other biochemical parameters were assessed at baseline and after 6 and twelve months of treatment.

Results:

There were no statistically significant differences between the levels of bone turnover markers before and 6 months after statin implementation (P > .05) - for all patients or subgroups according to statin use. Analysis of the results showed that after 12 months, there was a statistically significant decrease in N-terminal propeptide of procollagen type I concentration in all subjects (P = .004). By statin subgroup, a statistically significant decrease in N-terminal propeptide of procollagen type I was observed only in patients receiving rosuvastatin (P = .012) and not in those receiving atorvastatin (P = .25). Moreover, changes in bone turnover markers did not correlate with changes in lipid concentrations.

Conclusions:

These results may indicate the superiority of atorvastatin over rosuvastatin in inhibiting adverse changes in bone turnover in postmenopausal women. Confirmed by studies involving a larger population, the observed differences might find particular applications in clinical practice, and the choice of atorvastatin over rosuvastatin for women could be considered in the early postmenopausal period to reduce the risk of osteoporosis and subsequent osteoporotic fractures.

1. Introduction

Dyslipidemia is a major modifiable risk factor for atherosclerotic cardiovascular disease, which is the leading cause of death worldwide.^[1] In Europe, atherosclerotic cardiovascular disease is responsible for more than 4 million deaths every year.^[2] Statins are the first-line treatment for dyslipidemia. They act by specific, competitive, and reversible inhibition of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase in hepatocytes, leading to an inhibition of cholesterol synthesis in hepatocytes and increased lipoprotein uptake from the blood through increased expression of low-density lipoprotein receptors.^[2] Studies have shown that in addition to the beneficial lipid-lowering effect, statins also exhibit a number of pleiotropic effects that may contribute to the reduction of atherosclerosis and cardiovascular risk, as well as find applications in other diseases.^[2] We were particularly interested in reports of the pleiotropic effects of statins on bone tissue.^[3] In recent years, the number of reports regarding the effects of statins on bone tissue and the reduction in the risk of osteoporotic fractures has increased.^[4] The findings of published scientific studies indicate the possibility of using this effect in the prevention or adjuvant treatment of osteoporosis, which is becoming a serious health and epidemiological threat, mainly due to the aging of the population, affecting the quality and length of life.^[5,6]

The most common form of osteoporosis is postmenopausal osteoporosis.^[7] It is estimated that in the first 5 years after menopause, women lose 10% to 20% of their bone mass.^[8] Therefore, introducing interventions during this accelerated bone turnover period seems particularly important.

The gold standard in osteoporosis diagnosis is bone densitometry, which allows bone mineral density (BMD) to be assessed.^[5] Bone is a metabolically active tissue, and currently, we can determine changes in bone turnover even after about 3 months from the introduced intervention by measuring bone turnover markers (BTMs). The most useful BTMs include bone formation osteoblast-derived products and the bone resorption products of collagen degradation. Current recommendations indicate the significance of the C-terminal telopeptide of type I collagen (CTX-I) as a bone resorption marker and the N-terminal propeptide of procollagen type I (PINP) as a marker of bone formation.^[9]

The direct effect of statins on the bone tissue is complex. Studies have shown an increased expression of the bone morphogenetic protein 2 (BMP-2) gene, which increases bone synthesis.^[10] The exact mechanism by which statins increase bone formation is not fully understood. One possibility is that small prenylated proteins, byproducts of the mevalonate pathway, negatively regulate BMP-2 expression. By inhibiting the mevalonate pathway and preventing prenylation, BMP-2 expression may be increased, resulting in increased proliferation and differentiation of osteoblasts, followed by enhanced bone formation.^[11]

In in vitro studies, statins have also been shown to inhibit osteoclast activity directly. Like bisphosphonates, first-line drugs for osteoporosis treatment, statins inhibit HMG-CoA reductase in the cholesterol metabolism pathway (Fig. 1).^[11]

Figure 1.

Cholesterol biosynthesis. Mechanism of action of statins and bisphosphonates.

This indirectly inhibits protein prenylation, which may impair osteoclast functions.^[12] Statins may also stimulate an increase in osteoprotegerin (OPG) expression, which inhibits osteoclast activity. Atorvastatin treatment of primary osteoblasts resulted in elevated levels of OPG.^[13] By binding the receptor activator of nuclear factor kappa-Β ligand (RANKL), OPG blocks the binding of RANKL to the receptor activator of nuclear factor kappa-B. This results in the inhibition of osteoclast activity. The possible mechanisms by which statins affect bone turnover are summarized below (Fig. 2).

Figure 2.

Possible ways of statin affecting bone turnover. BMP-2 = bone morphogenetic protein 2, Co-A = coenzyme A, HMG-CoA = 3-hydroxy-3-methyl-glutaryl-coenzyme A, OB = osteoblast, OC = osteoclast, OPG = osteoprotegerin, RANK = receptor activator of nuclear factor kappa-B, RANKL = receptor activator of nuclear factor kappa-B ligand.

In the context of the pleiotropic effects of statins, their physicochemical properties, including lipophilicity, determine the distribution and bioavailability of statins to other organs.^[14]

This study aimed to compare the 2 most commonly used high-intensity statins on bone turnover in early postmenopausal women. Our study hypothesized that after the implementation of atorvastatin and rosuvastatin, we would observe a beneficial effect on bone turnover as measured by the concentration of BTMs and that the effect may be more pronounced with atorvastatin as a lipophilic statin than rosuvastatin as a hydrophilic statin. To the best of our knowledge, this is the first study to directly compare the effects of atorvastatin and rosuvastatin on recommended BTMs in postmenopausal women. Confirmation of our hypothesis could be used in clinical practice and initiate the selection of targeted therapy that would additionally protect against common and serious postmenopausal osteoporosis.

2. Materials and methods

2.1. Study population

Thirty-four postmenopausal women aged < 65 years (mean [SD] age, 59.2 [5.46] years) with newly diagnosed dyslipidemia requiring statin therapy were selected for the study. This age range was specified due to increased bone turnover during this period and fewer comorbidities that would modify cardiovascular risk by affecting the required statin dose and could significantly affect bone turnover. Patients were recruited from the Department of Internal Medicine, Metabolic Diseases & Hypertension, Poznań University of Medical Sciences, and from the outpatient clinic at the hospital. The exclusion criteria were body mass index <18 kg/m² and >35 kg/m²; chronic kidney disease (eGFR < 30 mL/min); decompensated endocrine diseases; diabetes; anorexia nervosa; absorption disorders; chronic obstructive pulmonary disease; asthma; aminotransferases 3 times greater than the normal upper limit; hematological diseases; rheumatoid arthritis; active neoplastic disease; smoking; confirmed osteoporosis requiring pharmacological treatment; and chronic use of drugs such as systemic corticosteroids, antiepileptic drugs, heparin, or oral anticoagulants.

2.2. Study protocol

Patients were randomly assigned to receive a statin drug. Seventeen women (50%) received rosuvastatin, and 17 (50%) received atorvastatin. Statins were initiated at standard doses of 5 to 10 mg of rosuvastatin and 20 mg of atorvastatin (the patients were at low or moderate cardiovascular risk, requiring the reduction of LDL-C by 30%–50%). Each patient underwent blood tests 3 times: before statin initiation and after 6 and 12 months of treatment. Blood was collected via venipuncture to assess the concentrations of lipids total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, alkaline phosphatase, 25-hydroxyvitamin D, creatinine, alanine aminotransferase, aspartate aminotransferase (AST), calcium, and inorganic phosphates. Blood was also collected and stored to assess the levels of BTMs: CTX-I and PINP. The levels were measured in early morning fasting blood specimens. Serum was separated from cells within 3 hours of blood collection, and then samples were immediately frozen. The levels of CTX-I (IDS, Boldon, UK) and PINP (Cloud-Clone Corp., Houston, USA) were quantified using commercially available enzyme-linked immunosorbent assay kits, following the manufacturer instructions. These assays employ the competitive inhibition enzyme immunosorbent technique with evaluated intra-assay precision CTX-I CV = 3.97% and PINP CV = 5.01% (in accordance with the manufacturer instructions CV < 10%). Routinely used biochemical methods measured the remaining parameters. The patients were asked to maintain a consistent diet and physical activity during the study. This was verified in a socio-demographic survey conducted at each stage of the study, using, among others, questions about diet and the International Physical Activity Questionnaire.

The Bioethics Committee of Poznań University of Medical Sciences approved the study protocol (number 1292/18) and informed consent was obtained from all the subjects.

All the recruited patients underwent laboratory tests performed before statin initiation. Twenty-two patients came for the examination after 6 months (11 taking atorvastatin and 11 taking rosuvastatin). Two patients were excluded due to diagnosed osteoporosis requiring appropriate treatment, 5 patients discontinued statin therapy, and 5 patients did not attend the scheduled follow-up visit. After 12 months, control laboratory tests were performed in 16 women (11 taking rosuvastatin and 5 taking atorvastatin); 6 patients did not attend a follow-up visit. The test results of patients excluded and dropped out of the study were not included in the statistical analysis (paired t-test and Pearson correlation).

2.3. Statistical analysis

Descriptive statistics were calculated for all the parameters. The normality of the parameter distribution was checked using the Shapiro–Wilk test. The paired t-test was used for the dependent samples. The results before and after the initiation of statin therapy were compared separately for the 6th and 12th months. In addition, the analysis was performed separately for all subjects and by the statin used. Data were also analyzed using Pearson correlation test for determining correlations. P values below .05 were considered significant.

Statistical analyses were performed using the IBM SPSS Statistics 26 package.

3. Results

Table 1 presents the basic clinical data of the study groups. There were no significant differences in the examined parameters between the compared groups.

Table 1.

Characteristics of the atorvastatin and rosuvastatin groups.

	Atorvastatin				Rosuvastatin				P
	n	M	Me	SD	n	M	Me	SD
Age (yr)	17	58.41	60.00	5.35	17	58.88	60.00	5.98	.810
Body mass (kg)	17	73.06	67.00	16.06	17	76.12	74.00	17.42	.598
Height (cm)	17	164.06	164.00	4.51	17	162.53	160.00	7.42	.474
BMI (kg/m2)	17	27.06	25.26	5.14	17	28.32	29.64	5.56	.498
Waist circumference (cm)	17	92.41	88.00	17.35	17	92.00	98.00	14.76	.941
Hip circumference (cm)	17	106.06	105.00	9.34	17	107.76	105.00	11.43	.637
Waist hip ratio	17	0.87	0.85	0.10	17	0.85	0.86	0.08	.639
TC (mmol/L)	17	6.46	6.35	1.13	17	6.31	6.10	1.10	.710
LDL-C (mmol/L)	17	4.30	4.24	1.16	17	3.92	3.88	0.79	.269
HDL-C (mmol/L)	17	1.70	1.67	0.50	17	1.52	1.42	0.40	.237
TG (mmol/L)	17	1.82	1.36	1.08	17	1.81	1.46	1.12	.990
Creatinine (umol/L)	17	68.95	69.00	13.84	17	63.01	62.00	7.58	.150
ALT (U/L)	17	30.59	26.00	23.74	17	35.00	25.00	20.89	.569
AST (U/L)	17	24.47	21.00	14.98	17	27.82	24.00	9.78	.445
Calcium (mmol/L)	17	2.48	2.50	0.13	17	2.44	2.47	0.20	.438
Phosphates (mmol/L)	17	1.33	1.25	0.24	17	1.24	1.23	0.13	.219
25(OH)D (ng/mL)	17	18.25	18.45	5.48	17	21.44	20.15	10.94	.306
ALP (U/L)	17	70.00	69.00	20.24	17	78.59	75.00	21.22	.252
PINP (ng/mL)	17	10.08	9.74	2.55	17	11.15	10.81	3.05	.292
CTX-I (ng/mL)	17	0.42	0.42	0.20	17	0.35	0.38	0.17	.281

25(OH)D = 25-hydroxyvitamin D, ALP = alkaline phosphatase, ALT = alanine aminotransferase, AST = aspartate aminotransferase, BMI = body mass index, CTX-I = C-terminal telopeptide of type I collagen, HDL-C = high-density lipoprotein cholesterol, LDL-C = low-density lipoprotein cholesterol, PINP = N-terminal propeptide of procollagen type I, SD = standard deviation, TC = total cholesterol, TG = triglycerides.

We investigated how the use of statins affected bone metabolism by assessing CTX-I and PINP levels. Table 2 shows the tested parameters at baseline and after 6 and twelve months of statin treatment. The results are presented separately for all subjects and by the type of statin used.

Table 2.

BTMs results after 6 and 12 mo of statin treatment.

			Before treatment		After treatment
			Mean	SD	Mean	SD	P value
After 6 mo of treatment	All patients	PINP, ng/mL	10.57	2.89	10.31	2.77	.77
		CTX-I, ng/mL	0.37	0.20	0.34	0.18	.43
	Atorvastatin	PINP, ng/mL	9.97	2.20	10.62	2.96	.51
		CTX-I, ng/mL	0.42	0.22	0.30	0.14	.11
	Rosuvastatin	PINP, ng/mL	11.16	3.45	10.00	2.68	.44
		CTX-I, ng/mL	0.33	0.17	0.37	0.22	.37
After 12 mo of treatment	All patients	PINP, ng/mL	11.04	3.09	8.14	2.78	.004
		CTX-I, ng/mL	0.33	0.17	0.36	0.21	.41
	Atorvastatin	PINP, ng/mL	10.77	2.46	9.02	4.47	.25
		CTX-I, ng/mL	0.33	0.19	0.30	0.12	.78
	Rosuvastatin	PINP, ng/mL	11.16	3.45	7.74	1.74	.012
		CTX-I, ng/mL	0.33	0.17	0.39	0.24	.14

BTMs = bone turnover markers, CTX-I = C-terminal telopeptide of type I collagen, PINP = N-terminal propeptide of procollagen type I, SD = standard deviation.

There were no statistically significant differences between the levels of BTMs (whether for bone formation markers PINP or for bone resorption marker CTX-I) before and 6 months after statin implementation (P > .05) - for all patients or subgroups according to statin use. However, analysis of the results showed that after 12 months, there was a statistically significant decrease in PINP concentration in all subjects (P = .004). In the statin subgroup, a statistically significant drop in PINP was observed only in patients receiving rosuvastatin (P = .012) and not in those receiving atorvastatin (P = .25).

To exclude the possible influence of changes in lipids on BTMs, an analysis was carried out to check whether the change in the value of lipid concentration was related to the change in the value of 2 parameters of bone turnover: CTX-I and PINP. Comparisons were made between all 3 measurements: changes after 6 months, after 12 months, and between 6 and 12 months. Table 3 presents the results of these analyses.

Table 3.

Correlations of changes in C-terminal telopeptide of type I collagen and N-terminal propeptide of procollagen type I values with changes in lipid concentrations.

	After 6 mo		After 12 mo		Difference between 6 and 12 mo
	Δ CTX-I	Δ PINP	Δ CTX-I	Δ PINP	Δ CTX-I	Δ PINP
Δ TC	0.04	−0.02	0.04	−0.32	0.10	−0.09
Δ LDL-C	0.10	−0.16	0.11	−0.27	0.04	−0.11
Δ HDL-C	0.17	0.08	−0.09	−0.16	−0.13	0.07
Δ TG	−0.26	0.14	−0.21	0.10	0.00	0.03

No statistically significant results were obtained.

Correlation was assessed in all 3 measurements - change after 6 mo, after 12 mo and between 6 and 12 mo.

Δ A change from the baseline till the specific measurement.

CTX-I = C-terminal telopeptide of type I collagen, HDL-C = high-density lipoprotein cholesterol, LDL-C = low-density lipoprotein cholesterol, PINP = N-terminal propeptide of procollagen type I, TC = total cholesterol, TG = triglycerides.

The analysis showed no statistically significant differences. This means that the changes in CTX-I and PINP values were not dependent on the changes in lipid concentrations.

4. Discussion

Despite several years of research on the effects of statins on bone turnover, very few conclusive results have been obtained. There has also been a lack of studies directly comparing high-intensity, fourth-generation statins. A comparison of the effects of these statins appears to be particularly important, as they differ in their physicochemical properties. In the context of the pleiotropic effects of statins, their physicochemical properties determine their distribution and bioavailability to other organs.^[14] Hydrophilic substances enter the cells via active transport. They are also more hepatoselective and have less potential for uptake by the peripheral cells. Lipophilic substances, on the other hand, enter the cells by passive diffusion.^[15] Easy penetration into tissues may result in more side effects but also in the inhibition of endogenous cholesterol synthesis in extrahepatic tissues and potentially greater possibility of pleiotropic effects.^[14] Despite the relatively low bioavailability of statins in bone, lipophilic statins may have a greater ability to penetrate bone cells than hydrophilic statins.^[16] In vitro studies also showed different effects of statins on bone tissue depending on the lipophilicity of the statin - independent of the distribution of the drug to tissues. Sugiyama et al proved that lipophilic statins (compactin and simvastatin), but not hydrophilic statin (pravastatin), selectively induce BMP-2 in osteoblastic cells by inhibiting HMG-CoA reductase.^[17] Different results were obtained by Steinberg et al, who showed that hydrophilic statins administered in vitro directly to bone tissue may increase bone proliferation and bone mineralization in cell lines, while the lipophilic statins may inhibit the mineralization process and induce cell death, contributing to a decrease in bone density and a greater risk of fractures.^[18]

In postmenopausal women, bone turnover accelerates due to decreased circulating estrogen.^[19] In peri-menopausal women, PINP values have been shown to decline gradually after the age of 59.^[20] Estrogens have been reported to directly modulate the differentiation of stromal cells into osteoblasts, thereby contributing to increased bone synthesis.^[21] Loss of bone mass in postmenopausal women thus results from an imbalance between bone resorption and bone synthesis, with bone formation processes failing to keep up with bone resorption processes.

In our study, a statistically significant decrease in the bone synthesis marker (PINP) concentration was observed among all subjects (at 12 months), but divided into statin subgroups, this decrease was significant only among patients treated with rosuvastatin. No decrease in bone osteoblastic activity, as measured by PINP, was observed in the atorvastatin group, which could indicate a more beneficial effect of the lipophilic statin.

The greater decrease in osteoblastic activity in patients treated with rosuvastatin than atorvastatin may be due to the hydrophilic nature of rosuvastatin and its poorer penetration into peripheral tissues. Atorvastatin, reaching peripheral tissues, including bone tissue, could increase the osteoblastic activity of osteoblasts, contributing to the inhibition of the postmenopausal decline in osteoblastic activity. This would confirm the previously described mechanisms of the possible influence of statins on the osteoblastic activity of bone tissue.^[10,11]

There are also reports in the literature that lipophilic statins (such as simvastatin) have a more beneficial effect on bone tissue than hydrophilic statins (such as pravastatin). Hernandez et al found higher BMD values in women taking statins than in those without treatment, but only for lipophilic statins.^[22] In addition, a meta-analysis by Uzzan et al found that the positive effect of statins on the BMD of the hip and femur was caused by the lipophilic statins used (simvastatin and lovastatin).^[23] Changes in PINP and CTX-I values under the influence of simvastatin (in the initial dosage of 40 mg/day, which was allowed to be increased to 80 mg if the initial dosage failed to meet accepted target lipid levels) have been assessed by Chuengsamarn et al The effects of statins (simvastatin) and other lipid-lowering drugs (fibrates) on selected BTMs were compared. The study population included both women and men. BTM levels were measured at the start of treatment and then at 3-month intervals for up to 18 months of therapy. The PINP levels after 18 months of treatment were significantly higher in the statin group. The CTX-I levels were significantly lower during statin therapy. These changes were statistically significant, whereas no statistically significant difference was observed in the group treated with other lipid-lowering drugs.^[24] However, in a double-blind, placebo-controlled study in postmenopausal women, 52 weeks of treatment with other lipophilic statin-atorvastatin did not show significant differences in the concentrations of the assessed BTMs, including CTX-I and PINP. The levels were evaluated at baseline and after 52 weeks of treatment. There were also no statistically significant differences between the groups treated with atorvastatin and placebo.^[25] The discrepancies in the results obtained may stem, among other things, from using different statins at different doses, for different durations, in populations of different age and gender, and from determining various markers of bone turnover. In addition, many other factors influence bone turnover, hence the need to verify the obtained data on as uniform and large a group of patients as possible. Our study compared the 2 strongest and most frequently used statins on the currently recommended markers of bone turnover, which should shed light on the purpose and direction of further research on the impact of statins on bone tissue.

Our study also showed no correlation between BTMs and lipid concentration changes. This may suggest a pleiotropic effect of statins, independent of the effect of statins on lipids. Such correlation was also examined by Majima et al.^[26] This study demonstrated that changes in the assessed markers of bone synthesis and resorption (bone-specific alkaline phosphatase and N-terminal telopeptide of type I collagen) during atorvastatin treatment did not correlate with the resulting changes in lipid levels.

Statins have been repeatedly demonstrated to have broad pleiotropic effects, that is, independent of their lipid-lowering effect. Extensive research on the impact of statins on the basic biological mechanisms of the atherosclerotic process shows that, in addition to their beneficial effect in lowering lipid levels, they also have many other activities that may contribute to the reduction of atherosclerosis and cardiovascular risk and may also be used in other disease entities. Statins mainly have anti-inflammatory and antioxidant effects and influence the normalization of endothelial function. Statins are also responsible for inhibiting other elements of the atherosclerotic process, such as an increase in the number of macrophages or the migration and proliferation of smooth muscle cells.^[27] The pleiotropic effects of statins are confirmed by in vitro and in vivo animal studies, and work on their clinical significance is still ongoing.^[3]

Some studies have shown that the effect of statins on bones may be pleiotropic, independent of changes in lipid concentrations.^[17,28] Sugiyama et al conducted an in vitro study on human osteosarcoma cells. It was found that compactin and simvastatin activated the BMP-2 promoter; such osteoblastic activity was not demonstrated for pravastatin. Importantly, this study found that the induction of BMP-2 promoter activity was a result of the HMG-CoA reductase inhibition and the treatment of the cells with cholesterol did not alter BMP-2 promoter activity.^[17]

In our area of study, clinical trials on rosuvastatin are still lacking. There is also a shortage of studies directly comparing atorvastatin and rosuvastatin, the 2 most commonly prescribed statins.

Our study indicated that atorvastatin may better inhibit postmenopausal bone osteoblastic decline than rosuvastatin. However, this study had some limitations, especially the small number of participants. During the COVID-19 epidemic, it was challenging to create a sufficiently large study group, mainly because of limitations in the functioning of the health services. The imposed restrictions contributed to the reduction in scheduled admissions to our department and a significant decrease in visits to the outpatient clinic due to the switch to the recommended mode of providing medical advice in the form of teleconsultations. The small sample size of the study group was also affected by general reluctance (especially among women) to take statins and low adherence to statin therapy. The pandemic was also the reason some patients did not report for scheduled follow-up visits, during which control laboratory tests were performed. Although there was a difference in bone turnover changes among patients with different statin treatment, these findings should be interpreted cautiously. Changes in bone turnover are dynamic at this age, and it is difficult to minimize the effect of many factors that influence it in the study, especially in a small study group. Further studies are needed to determine whether the superiority of atorvastatin over rosuvastatin in early postmenopausal women found in our research is clinically relevant.

5. Conclusions

In conclusion, to the best of our knowledge, this is the first study comparing the 2 most commonly prescribed high-intensity statins in terms of recommended BTMs. These findings may indicate the superiority of atorvastatin over rosuvastatin in inhibiting adverse changes in bone turnover. Confirmed by studies involving a larger population, the observed differences might find specific applications in clinical practice, and the choice of atorvastatin over rosuvastatin for women could be considered in the early postmenopausal period. When initiating lipid-lowering therapy, choosing a statin with a positive effect on bone metabolism may be a simple tool to reduce the risk of osteoporosis and subsequent osteoporotic fractures. Our findings warrant additional studies comparing the effects of atorvastatin and rosuvastatin on recommended BTMs on a larger and as uniform as possible cohort of postmenopausal women.

Author contributions

Conceptualization: Anna Braszak-Cymerman, Marta K. Walczak, Mary-Tiffany Oduah, Wiesław Bryl.

Data curation: Anna Braszak-Cymerman, Marta K. Walczak, Mary-Tiffany Oduah.

Formal analysis: Anna Braszak-Cymerman, Marta K. Walczak, Aleksandra Ludziejewska.

Funding acquisition: Wiesław Bryl.

Investigation: Anna Braszak-Cymerman, Marta K. Walczak, Aleksandra Ludziejewska.

Methodology: Anna Braszak-Cymerman, Marta K. Walczak, Mary-Tiffany Oduah, Wiesław Bryl.

Project administration: Anna Braszak-Cymerman, Marta K. Walczak, Wiesław Bryl.

Resources: Wiesław Bryl.

Supervision: Marta K. Walczak, Wiesław Bryl.

Writing – original draft: Anna Braszak-Cymerman, Marta K. Walczak.

Writing – review & editing: Anna Braszak-Cymerman, Marta K. Walczak, Mary-Tiffany Oduah, Aleksandra Ludziejewska, Wiesław Bryl.