## 2 Materials and Methods  
The study received the Ethical Commission approval from the University of Medicine and Pharmacy Cluj-Napoca (no. 229/22/06/2020) and was performed in a single institution. The sample size was calculated using data from a similar study, an alpha type I/II error rate of 0.05, and a power of 80% [7]. The inclusion criteria were represented by age >18 years old, primary osteoarthritis, and cementless total hip replacement, while the exclusion criteria were represented by patients not willing to undergo the experiment, liver failure, allergy to simvastatin or its other compounds, allergy to alendronate or its other compounds, use of drugs contraindicatedwith the use of alendronate or simvastatin, as well as previous use of bisphosphonates and statins. Once the patients were admitted to the hospital for the standard preoperative screening tests (including blood tests), informed consent was obtained. All patients included in the study underwent a preoperative DEXA scan to determine the bone mineral density (BMD) using a DEXA GE Prodigy Advance device. Osteoporosis was diagnosed when a T score of \(-2.5\) or less was obtained. An additional spine protocol was also applied to the affected hip for further analysis, as is described. Only patients with osteoporosis were further enrolled in the study. If the patients had hyperlipidemia diagnosed during the preoperative screening tests, they were allocated to group II (simvastatin) until a number of 15 patients was reached. The rest of the patients were randomly allocated to group I (alendronate) or group III (control) until a number of 15 patients was obtained in each group. When group II had reached 15 patients, the following patients with hyperlipidemia were randomly assigned to group I (alendronate) or group III (control) until a number of 15 patients were allocated within each group. We also collected the following data from each of the patients: sex, age, body mass index (BMI), history of smoking, history of diabetes, and hypertension. Blood serum was harvested preoperatively and used for the determination of beta cross-laps (\(\beta\)-CTx) and alkaline phosphatase (ALPL) blood test analysis. Two Enzyme-linked immunosorbent assay (ELISA) kits were used for the determination of ALPL (Cat. No. E-EL-H2598) and B \(\beta\)-CTx (Cat. No. E-EL-H0960) levels in human serum (sau era Plasma). Both ELISA kits were purchased from Elabscience (Elabscience Biotechnology Inc., Huston, TX, USA. The plate absorbances were read at 450 nm using a TECAN SPARK10M (TECAN, Austria GmbH, Grodig, Austria), and the results were analyzed compared to the standard curve). The samples were handled according to the protocol, and the results were expressed as pg/mL of each molecule of interest. All of the surgeries were performed in the same center, by the same surgeon, using the lateral approach and the same implants (Zimmer Biomet, Warsaw, IN, USA). Tranexamic acid was administered postoperatively, as previously described [8]. Moreover, all of the patients followed the same postoperative protocol in terms of anticoagulants, painkillers, antibiotic prophylaxis, and physical therapy exercises. In terms of weight-bearing, the patients were not allowed to bear full weight for 6 weeks postoperatively. In addition, patients in group 1 (alendronate) received 5 mg of alendronate orally daily for 8 weeks, starting on day 1 postoperatively, while group 2 (simvastatin) received 20 mg of simvastatin orally daily for 4 weeks, starting on the first postoperative day, followed by 40 mg daily for 4 weeks. DEXA scans were performed postoperatively at 4 and 8 weeks postoperatively, and the regions were scanned according to Gruen zones (1-7), as previously described [9]. An example of Gruen zone calculation is seen in Figure 1. We used the spine protocol for a better analysis.