Background Spinal cord injury (SCI) has been associated with a marked increase in bone loss and bone remodeling, especially short-term after injury. However, the pathogenesis and clinical management of this process remain unclear, as well as the role of the key regulators of bone remodeling, the OPG/RANKL system.
Objectives To analyze the role of the regulators of bone remodeling, OPG and RANKL, in the bone loss associated with recent SCI as well as the effect of antiosteoporotic therapy with denosumab in these bone regulators in a prospective study.
Methods Twenty-three male patients (aged 18 - 67 years [mean 36 ± 16 years]) with recent (<6 months) complete SCI were prospectively included (43.5% paraplegic, 56.5% tetraplegic). Patients were followed every 6 months. All patients received calcium and vitamin D supplementation. Antiosteoporotic therapy with denosumab was recommended when patients developed densitometric osteoporosis during follow-up. Serum levels of OPG and RANKL (Biomedica, Vienna, Austria), bone turnover markers (PINP, bone ALP, sCTX) and bone mineral density (BMD) at the lumbar spine and total hip were assessed at baseline (99±30 days after SCI), prior to initiating antiosteoporotic treatment (14±4 months post-SCI) and during antiosteoporotic therapy with denosumab (6 months after initiating treatment). The results were compared with a healthy control group.
Results At baseline, SCI patients showed a significant increase in RANKL serum levels compared to controls (3.4±1.7 vs. 2.3±1.6 pg/mL, p=0.022) which correlated with days-since-SCI (r=0.589, p=0.005) and became undetectable after denosumab treatment in 67% of the patients (p=0.001). OPG serum levels were similar to controls at baseline (87.7±38.7 vs. 71.7±25.4, p=0.1) and did not change with denosumab treatment. No differences were observed in RANKL and OPG levels on comparing tetraplegic vs. paraplegic patients. Neither were RANKL or OPG levels related to the increase in bone loss and bone turnover markers after SCI. Patients with undetectable RANKL serum levels after denosumab treatment did not present further sublesional bone loss but increased total hip BMD (+2.5±1.3%, p=0.005), and bone markers markedly decreased (PINP: -53%, p=0.007; sCTX: -68%, p=0.005).
Conclusions This study shows that short-term after SCI there is an increase in RANKL serum levels which become undetectable after denosumab treatment. The preventive effect of denosumab on sublesional bone loss further suggests a contributory role of RANKL in this clinical process.
Acknowledgement Work funded by a Grant from the SEIOMM (Spanish Society for Bone and Mineral Research).
Disclosure of Interest None declared
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