Bone diseases are considered a serious problem in Kuwait; the proportion of osteoporosis among the Kuwaiti population is relatively high if compared to international standards [23]. This problem is more apparent in RTR because of transplant complications and medications used before and after transplantation. In Hamed Al-Essa organ transplant center, more than 40% of the patients suffer from osteoporosis or osteopenia, those patients need frequent follow-up to prevent any complications associated with these conditions. Twenty percent of transplant patients develop a fracture in the first 5 years after transplant [24]. For that, it is important to use safe and effective medications to treat the underlined problem and protect the transplanted organ.
After one year of treatment, denosumab improved both spinal and hip T-score values in comparison with ibandronate, this result is consistent with previous studies that have demonstrated the preferable effect of denosumab over bisphosphonate in RTR. Mckee et al. showed a greater increase in both spinal and femoral neck BMD (0.045 and 0.022 g/cm2, respectively) in denosumab group over the bisphosphonate group after almost 3 years of follow-up in RTR [28]. Besides, denosumab improved both spinal and hip T-score values significantly by 0.42 and 0.1, respectively, in the study performed by Bonani et al. [22]. Besides, Tillmann et al. did not detect a significant improvement in BMD after using ibandronate in RTR as compared to the control group [22, 25, 26].
Bisphosphonates, calcium, and vitamin D have been previously proved to decrease the rate of bone loss after transplant, the same combination failed to increase the bone mass at all sites in RTR [8, 20, 27, 28]. In contrast to ibandronate that decreases osteoclast activity, denosumab acts mainly by inhibiting RANKL system. This unique mode of action is specifically useful in RTR because of the activation of the RANKL system by glucocorticoids and calcineurin inhibitors, which may explain the ability of denosumab to increase bone mass in RTR who use these medications in high doses after transplant [29]. At the same time, the 6 monthly use of denosumab injection is a less troublesome option for RTR who use a lot of medications to prevent rejection of the transplanted organ or treat other conditions like hypertension and diabetes [30].
The use of ibandronate in this study was more associated with GIT side effects like stomach upset and vomiting, which is a well-known bothersome effect of using oral bisphosphonates in general [31]. Although its use was more tolerable, the reported hypocalcemia episodes were significantly higher with denosumab. These episodes were not severe and did not need any interventions except increasing the oral calcium dose. Close monitoring of calcium levels is likely needed with stage 4 and 5 chronic kidney disease and new denosumab patients because they are more susceptible to be affected with hypocalcemia [32].
The encouraging results of denosumab in RT patients may give the nephrologists a reliable option to be used safely and effectively after, or even directly after, transplantation. Bonanai et al. used denosumab in de novo kidney transplant patients with the auspicious results, as it increased areal bone mineral density (aBMD) at all sites, improved cortical volumetric bone mineral density (vBMD), and decreased blood and urine bone turnover biomarkers significantly [22]. Other medications used for osteoporosis like ibandronate failed to demonstrate such results. In addition, ibandronate is not recommended in patients with CrCL less than 30 ml/min [33].
The study has some limitations like the inability to assess bone turnover biomarkers like β-CTX and urine deoxypyridinoline. Also, the assessment period (1 year) was not long enough to evaluate long term efficacy and safety.