Studying Risk Factors Association with Osteoporosis in Post Kidney Transplantation Patients

Osteoporosis that associate with kidney transplantation is an important cause of morbidity to the patients that warranted extensive study about possible causes of osteoporosis in order to implement several steps to reduce this risk. The current work aimed to investigate possible association between post kidney transplant immunosuppression therapy type and developing the osteoporosis and evaluate the bone mass by using dual X-ray absorptiometry (DXA) post-renalal transplant. A case-control, conducted in kidney transplant center – medical city complex for one year period (from October 2018 till April 2019), Seventy - (cid:977)ive kidney transplant patients were participated in the present study including (21 females & 54 males). All patients were exam-ined for their bone density using DEXA scan (T – score) and those with cut – point (cid:20) - 2.5 were diagnosed as having osteoporosis (lumber and hip bones were examined). The prevalence of osteoporosis and osteopenia was signi(cid:977)i-cantly higher in transplant patients compared to control for bone lumber and hip bone (for lumber bones: 33.3% vs 2.7%l for hip bones: 60% vs. 14.7%). T score was signi(cid:977)icantly lower in the transplant patients compared to control for both lumber (-1.9 (cid:6) 0.8 vs. -1.1 (cid:6) 0.7) and hip bones (-2.3 (cid:6) 0.9 vs -1.3 (cid:6) 0.8). In logistic regression analysis; only gender and BMI were the predictors of osteoporosis for spinal bone, while; the BMI and calcium were the predictors of osteoporosis for hip bones. In conclusion, Osteoporosis in post-renal transplant patients have a high rate of osteoporosis compared to the general popu-lation, post-renal transplant drugs (Cyclosporine, MMF, etc.) did not increase the risk of osteoporosis, and body mass index and female gender were risk factors for osteoporosis.


INTRODUCTION
Kidney function to maintain stable internal equilibrium by eliminating excess water, electrolytes, and other byproducts, through the formation of ultra iltrate from the plasma by the iltration action of glomerulus system, which can serve as a system for reabsorption or section of other materials and byproduct (Bailey et al., 2015).
The mainstay of treatment of ESRD is either dialysis (temporary solution), or a kidney transplant. Transplant results in a better outcome in comparison to dialysis (in terms of clinical and QOL bene-its) (Wolfe et al., 1999). However, transplant had its drawbacks, including low availability of kidney from donors, use of chronic immunosuppressant medications and others factors; these factors together with superiors outcome compared to dialysis lead to the development of criteria for selective candidates for the operation to include as many as possible patients to bene it from transplantation (Fritsche et al., 2000).
In order to prevent graft loss caused by an immune reaction, several protocols develop, these protocols will prevent acute rejection. Currently, reduction of side effects caused by these protocols become as important as their role in reducing the incidence of acute rejection. In the present time, intensive immunosuppression in the early stages of the transplant becomes a paramount, followed by maintenance protocol to reduce the risk of rejection (Wiseman and Cooper, 2015;Shawkat et al., 2018).
However, many of these drugs have a side effect that will result in more deterioration of bone density and osteoporosis. Osteoporosis is a disease that associated with low bone mass and density, micro architectural disruption, and increased skeletal fragility. After renal transplantation, there are changes in the normal bone remodeling system which will lead to more accelerated osteoporotic changes compared to normal individuals, while for transplantationrelated bone loss results from both an increase in the rate of resorption and a decrease in the rate of bone formation (Stein and Shane, 2013). The current work aimed to investigate possible association between post kidney transplant immunosuppression therapy type and developing the osteoporosis and evaluate the bone mass by using dual X-ray absorptiometry (DXA) post-renalal transplant.

Study design
This is a cross-sectional study of a cohort for patients who admitted to kidney transplant centermedical city complex for one year period (from October 2018 till April 2019).

Patients
Seventy -ive kidney transplant patients were participated in the present study, including (23 females & 52 males). The age range was (15 -65) years. Apparently, healthy thirty subjects were selected to participate as a normal group for comparison (control) including (35 females & 40 males). The age range of these subjects was (15 -65). The follow up of kidney transplant patients was made by specialist's surgeon.

Bone density assessment
DEXA scan was used for the assessment of bone density, with T -score ≤ -2.5 to de ine osteoporosis and between -1.0 to -2.5 to de ine osteopenia, according to WHO criteria (Ensrud and Crandall, 2017).

Laboratory procedure
A 5 ml venous blood sample from each participant were collected and then sent for laboratory analysis in the Medical City Complex campus, serum calcium, phosphate, ALP, vitamin D3, PTH, and albumin measurement were recorded. For serum calcium, PO4, ALP, and albumin spectrophotometry methods was used in the measurement of serum levels, while for vitamin D and PTH immune lorescent assay was used.

Statistical analysis
For assessment of continuous variables, independent t-tests was used, while for categorical variables chi-square test used, ordinal logistic regression analysis used to examine the risk of osteoporosis (in which the order of category from lowest to highest was normal bone, osteopenia, and osteoporosis). All analysis carried out using SPSS version 22.0.0 (Chicago, IL) and GraphPad Prism version 8.2.1 (San Diego, California USA), p-value considered when appropriate to be signi icant if less than 0.05.

RESULTS AND DISCUSSION
The study included 150 participants, mean age of patients was not signi icantly different in the study group compared to control (38.4±11.5 vs 44.9±6.6 years, respectively), with age range from 18 -64 years, for both control and study age group between 40 -49 years was the most common (40.4% and 26.7%, respectively). BMI was signi icantly lower in the study group compared to control (25.2±3.8 vs 27.0±7.5 kg/m 2 , respectively), 46.2% of the control was obese while 47.5% of the study group had normal BMI. There was no signi icant difference in gender between both groups, with male to female distribution rate (1.14:1 vs 2.26:1, respectively), as illustrated in Table 1.
The prevalence of osteoporosis and osteopenia was signi icantly higher in transplant patients compared to control for bone lumber and hip bone (see Table 3), also; T score was signi icantly lower in the transplant patients compared to control for both lumber and hip bones, as illustrated in Table 2 and Figure 1 and Figure 2. Only gender and BMI were the predictors of osteoporosis for spinal bone, as illustrated in Table 3.
The BMI and calcium were the predictors of osteoporosis for hip bone, as illustrated in Table 4.
Disturbances in bone metabolism are common complications that affect patients after successful renal transplantation. The usual method for assessing BMD by DXA scan in which osteoporosis de ined as T score ≥ -2.5 standard deviation (one standard deviation represent the average of young adult) (Rachner et al., 2011). BMD in patients who have undergone renal transplantation has been reported to decrease by a mean of 5.5% to 19.5% during the irst 6 months but only 2.6% to 8.2% between months 6 and 12 after surgery (Malluche et al., 2009).
In the present study mean age of transplant patients were 40.9 ± 12.2 years, with 73.3 % of them distributed between 39 -59 years, our indings were similar to those of Coco et al. (2003) study which included 59 kidney transplant patients with mean age of 45.5 ± 13 years (Coco et al., 2003), also in agreement with Walsh et al. (2009) (Smerud et al., 2012), also lower than other study with mean age of 50.7 ± 15.5 years for 49 control transplant patients (Torregrosa et al., 2010).
In this study, the prevalence of osteoporosis, osteopenia, and normal bone for spinal bone were 33.3%, 48.0%, and 18.7%; while for hip bone it was 60.0%, 30.7%, and 9.3%.
The high rate of osteoporosis that observed in this study can be explained by the long duration of transplantation that can will more progressive bone disease, also all patient received corticosteroids (CS) and for extended period of time, since CS is known to cause bone loss by its inhibitory effect on osteoblast cells, and activation of osteoclastic activity, reduction of Ca absorption from the GIT, enhance renal Ca excretion and increased section of PTH (Coco et al., 2003).
This can be explained by the lack of effect of CyA on bone, or since the decrease in BMD in transplant recipients is dif icult to evaluate because CyA  Sirolimus might impair bone formation by interfering with the proliferation and differentiation of osteoblasts and might contribute to the impairment of osteoclast-mediated bone resorption (Marcén et al., 2007). In the present study, there was no correlation between the use of sirolimus and osteoporosis, which is in agreement with other studies (Hsu et al., 2016).
Osteoporosis after kidney transplantation is multi factorial, while pathophysiologic mechanisms responsible for this condition are not completely elucidated. Pre-transplantation risk factors include the duration of dialysis, high or low parathormone (PTH) levels and preexisting bone disease.
Post-transplantation risk factors associated with bone loss and/or fractures are deceased kidney donor, immunosuppressive regimen choice (glucocorticoids, calcineurin inhibitors), and time since transplantation, hypophosphatemia and graft dysfunction. Additional risk factors such as postmenopausal status for women and presence of diabetes have been considered as possible culprits, in adjunction to the classical osteoporosis risk factors such as age and female gender (Dounousi et al., 2015).

CONCLUSIONS
Osteoporosis in post-renal transplant patients have a high rate of osteoporosis compared to the general population, Post-renal transplant drugs (Cyclosporine, MMF, etc.) did not increase the risk of osteoporosis, and Body mass index and gender were risk factors for osteoporosis.