Bisphosphonate therapy after liver transplant improves bone mineral density and reduces fracture rates: an updated systematic review and meta‐analysis

Abstract

Summary To investigate the efficacy of bisphosphonates and compare oral and IV formulations on bone mineral density (BMD) and fracture incidence in post‐orthotopic liver transplant (OLT) patients. Electronic databases were searched, and six RCTs and three cohort studies were included out of 711 articles. Main outcomes included post‐OLT BMD changes, fracture incidence, and treatment adverse reactions. Pairwise meta‐analysis was conducted for binary and continuous outcomes, while pooled fracture incidence utilized single‐arm meta‐analysis. Post‐OLT fracture incidence was reported in nine studies (n = 591). Total fracture incidence was 6.6% (CI: 3.4–12.4%) in bisphosphonate group and 19.1% (CI: 14.3–25.1%) in calcium and vitamin D group. Total fractures were significantly lower in patients on bisphosphonate, compared to calcium and vitamin D (n = 591; OR = 0.037; CI: 0.18–0.77; P = 0.008). Overall fractures were significantly lower in the oral group (n = 263; OR = 0.26; CI: 0.08–0.85; P = 0.02) but not in the IV group (n = 328; OR = 0.45; CI: 0.16–1.26; P = 0.129). Both oral and IV bisphosphonates are effective in reducing fracture incidence post‐OLT compared to calcium and vitamin D. Oral formulations may also have an advantage over IV in reducing bone loss and fracture incidence post‐OLT.

Changes in Serum Bone Metabolism Markers after Living Donor Liver Transplantation (LDLT) and Their Association with Fracture Occurrences

“…Patients who developed osteoporotic fractures after LDLT had higher baseline OPG, lower baseline RANKL and a higher OPG/RANKL ratio. A recent meta-analysis suggested that bisphosphonate therapy could reduce fracture rates in liver transplant recipients, but the fracture incidence was still as high as 6.6% even in the bisphosphonate group [30]. Based on our findings and published studies, we hypothesize that a relatively low but not extremely low systemic osteoclast activity level may be optimal to prevent osteoporotic fractures in LDLT recipients.…”

Risk factors for fractures following liver transplantation: a population-based cohort study

“…Chronic obstructive liver disease may interfere with vitamin D metabolism, leading to decreased uptake of vitamin D. In addition, cirrhosis has been shown to impair 25-hydroxylation of vitamin D, consequently resulting in significantly depressed levels of 25-hydroxyvitamin D3 [ 23 ]. Previous studies have reported that prophylactic bisphosphonate treatment is effective in preventing bone loss and fractures in liver transplant recipients [ 24 , 25 ]. In the present study, we found that the use of bone protective medications including bisphosphonates, vitamin D supplements and calcium supplements did not have a beneficial effect on decreasing the risk of fractures.…”

Bone pattern changes in post liver transplant patients using bisphosphonates

“…Hepatic osteodystrophy is a relevant complication in patients with advanced liver disease and transplant recipients, with fractures and osteoporosis being more common in the first year after transplant, corresponding to the greatest bone loss period. [6][7][8][9][10] The assessment of the bone bases is carried out using imaging tests, such as a panoramic x-ray of the jaw, which is a routine complementary examination in dental care. 10 The analysis of the mandibular córtex endosteum quality and the analysis of this same cortex at the level of the mental foramen are valuable techniques for evaluating bone signs of low bone mineral density.…”

“…Changes in bone metabolism may also occur as liver disease progresses. Hepatic osteodystrophy is a relevant complication in patients with advanced liver disease and transplant recipients, with fractures and osteoporosis being more common in the first year after transplant, corresponding to the greatest bone loss period 6–10 …”