INFLUENCE OF ALENDRONATE THERAPY ON THE RESULTS OF DENSITOMETRIC EXAMINATION AFTER IMPLANTATION OF TOTAL HIP ENDOPROSTHESIS

ВЛИЈАНИЕ НА АЛЕНДРОНАТНАТА ТЕРАПИЈА ВРЗ РЕЗУЛТАТИТЕ ОД ДЕНЗИТОМЕТРИСКОТО ИСПИТУВАЊЕ ПО ИМПЛАНТАЦИЈА НА ТОТАЛНА ЕНДОПРОТЕЗА НА КОЛКОТ Ilir Shabani1, Antonio Gavrilovski1, Vilijam Velkovski1, Nenad Atanasov1, Shaban Memeti2, Anila Belchishta1 1 University Clinic for Traumatology, Orthopedics, Anesthesiology, Reanimation and Intensive Care; Ss Cyril and Methodius in Skopje, Faculty of Medicine, Republic of North Macedonia 2 University Clinic for children’s susrgery; Ss. Cyril and Methodius University in Skopje, Faculty of Medicine, Republic of North Macedonia


INFLUENCE OF ALENDRONATE THERAPY ON THE RESULTS OF DENSITOMETRIC EXAMINATION AFTER IMPLANTATION OF TOTAL HIP ENDOPROSTHESIS
The development of aloarthroplasty of the hip is continuously rising. After implantation of a total cement-free hip endoprosthesis, often there is a periprosthetic femoral bone loss. Alendronate has been shown to be a potent inhibitor of bone resorption activity; it inhibits osteoclastic bone resorption, increases bone mass, and plays a significant role in post-implantation stabilization of the femur. The aim of this study was to determine the effect of alendronate on osteointegration of hip endoprosthesis.Material and methods: The study analyzed 10 patients operated on with implantation of a total cement-free hip endoprosthesis (THP). The included patients were examined by a radiographic method at 6 and 12 months and DXA method at 6 and 12 months. Results: The study showed differences in the values of bone mineral density and bone mineral content in the interval between 6 and 12 months in patients undergoing THP, and hence we can conclude that alendronate therapy after THP implantation reduced periprosthetic loss of bone mass and implant stiffening. Alendronate is a proven inhibitor of periprosthetic bone loss that occurs after prirmary impantation of a total cement-free hip endoprosthesis

Introduction
Implantation of cement-free endoprosthesis, as a method for functional reconstruction of the hip, ensures bone growth in irregular surfaces and achieves its stable biological fixation. 1,2 The implantation of cement-free implants depends on several basic factors: • the design of the applied implant, • the biological capacity of the entire anatomical segment where the implant is implanted • the biological potential of the organism as a whole. 3,4,5 Good primary fixation of both components (acetabular and femoral), elimination of all irritating components (physical, chemical, mechanical and biological) are prerequisites defined under the terms biostability and biocompatibility.
Following the experience in implantation of total hip prosthesis, the most common complication that occurs is aseptic loosening of the prosthesis components whose incidence increases over the postoperative time, forcing prosthesis reoperation.
One of the possibilities for postimplantation reduction of periprosthetic bone loss is the use of modern drug bisphosphonate therapy with alendronate. [6][7][8] Alendronate (alendronic acid -alendronate sodium) is a bisphosphonate drug that is a potent inhibitor of bone resorption activity. It inhibits osteoclastic bone resorption. Like other bisphosphonates, it is chemically linked to inorganic pyrophosphates and is an endogenous regulator of the bone metabolism. At the cellu-lar level, it enables reduction of bone metabolism, increases bone mass and confirms mineralization of the bone matrix. [9][10][11][12] Bisphosphonate therapy with alendronate at a therapeutic dose of 10 mg daily + 1000 mg calcium and vitamin D3 for 18 months provides opportunities for prevention of periprosthetic osteolysis, which is expected to make a significant progress in post-implant stabilization of implanted endoprosthetic implants and a risk of their premature loosening accompanied by all its consequences. [13][14][15] The first published experiences for the use of bisphosphonate therapy with alendronate in the direction of reduction of periprosthetic osteolysis showed that it resulted in a significant reduction in periprosthetic bone loss after primary THP implantation compared to the group of patients who did not undergo the above therapy. [16][17][18][19] In 2003 Nehme A. et al. examined the effect of alendronate on the reduction of periprosthetic bone loss over a period of two years. During that period, in the control group, the bone loss reached a plateau 6 months after the implantation of the total hip prosthesis measured by the DXA method and it reached 12.7% of bone loss at the end of the second year. In the alendronate group, there was no plateau; bone density continued to increase, and bone loss reached a maximum of 6.85% by the end of the second year. 20 In 2005, Tcing Hua et al. reduced periprosthetic osteolysis induced by residual implant particles in patients undergoing alendronate therapy. According to these authors, the mechanism of reduction of periprosthetic osteolysis consisted in an increase in osteoprotegerin, a protein produced by a direct secretion from osteoblasts. [21][22][23] In 2006, Li Hong-bin performing experimental analyses of animal models came to the realization of a significant increase in periprosthetic bone growth after oral administration of alendronate. [24][25][26] In all the above test results, periprosthetic bone reduction mainly occured in the first 6 months after implantation of a total cement-free hip prosthesis. In this regard, DXA studies have shown that patients with low preoperative values for bone mineral density tend to have the greatest bone loss after implantation of a total hip endoprosthesis. [27][28][29] The aim of this study was to evaluate the value of alendronate application in reducing the periprosthetic osteolysis after implantation of a total cement-free hip endoprosthesis.

Material and method
The clinical material included 10 patients treated at the University Clinic for Orthopedic Diseases with implantation of a total hip endoprosthesis in the period from 2016 to 2018 due to degenerative diseases of the hip.
All patients in the study were clinically and osteodensitometrically without visible signs of osteoporosis. All patients underwent spinal anesthesia with anterolateral hip approach, with standard verticalization 3 days after the operative treatment and a standard postoperative rehabilitation period. All were permanently treated with alendronate bisphosphonate therapy as well as standard vitamin therapy and calcium substitution therapy per os.
This study was based on a clinical trial using two diagnostic methods: native hip radiography and dual energy X-ray absorption (DXA). Densi- Native X-ray with marked Gruen zones tometric analysis refers to 7 Gruen zones of the femur, through which periprosthetic osteolysis is formed in the femur, after implantation of total hip prosthesis (THP) is assessed ( Fig.  1 and 2). The results of both examinations were obtained and analyzed at 6 and 12 months after the surgical intervention.

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The analysis consisted of comparing the results for BMD (bone mineral density) and BMC (bone mineral content) obtained at different time points.
In this initial phase of the study, ten patients were available and were treated with alendronate therapy. Bone mineral concentration (BMC) and bone mineral density (BMD) were determined in all of them at two time points: 6 months and 12 months from the beginning of alendronate therapy.
In each patient, BMC and BMD measurements were performed at the level of the seven Gruen zones-points (1, 2, 3, 4, 5, 6, and 7) (see Figure 1 and In each patient, we calculated the arithmetic means (averages) of the measured values of BMC and BMD in the seven points, especially after 6 months, and after 12 months.

Results
The age distribution of patients was 45-65 years, of which 7 were females and 3 males. These arithmetic means (averages) for all 10 patients are shown in Table 1. Furthermore Figure 3 shows the graphical comparison of the obtained values. It is evident that in all patients the BMC and BMD values were higher after 12 months of alendronate therapy, compared to the values after only 6 months. This supports the effectiveness of alendronate therapy in reducing bone loss after implantation of a total hip endoprosthesis.

Discussion
In our study, BMC and BMD values were found to be higher after 12 months of alendronate therapy compared to values after only 6 months. Studies investigating periprosthetic BMD have shown that the most significant bone loss occurs in the first 3 to 6 months after endoprosthesis implantation, followed by a period of stabilization during the first postoperative year. [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] Few studies have investigated the effect of alendronate on periprosthetic bone loss. A prospective randomized study examined 13 patients treated for coxarthrosis with a cement-free hip endoprosthesis. Patients were randomized to receive only calcium or calcium alendronate. This study showed that in patients treated with alendronate bone loss was significantly lower than in the control group (0,9% vs. 17.1% for proximal Gruen zones and 2.6% vs. 9.9% for all Gruen zones). 28 In our group of patients, the results have shown an increase in BMD in all Gruen zones for all patients individually over a period of 6 months (measured 6 and 12 months after surgery), indicating the benefit of alendronate in reducing periprosthetic osteolysis.
Our results regarding the values of BMD, but also BMC, support the potential benefit of alendronate in improving denture implantation, as studies show that the mechanism of action of alendronate is expressed through an increase in bone mass of the cortical and trabecular bones, with the largest increase being in the trabecular bone,