Bone Turnover Marker (BTM) Changes after Denosumab in Giant Cell Tumors of Bone (GCTB): A Phase II Trial Correlative Study

Abstract

Background: Giant cell tumors of bone (GCTB) are osteolytic tumors. Denosumab, a RANK-L inhibitor, is approved for GCTB. Data on serum bone turnover marker (sBTM) changes are lacking. We present a phase II correlative study on sBTMs in GCTB patients treated with denosumab. Methods: All GCTB patients receiving denosumab within a multicentre, open-label, phase 2 study were enrolled. Serum levels of carboxyterminal-crosslinked-telopeptide of type I collagen (s-CTX), alkaline phosphatase (ALP), bone-alkaline phosphatase (bALP), parathyroid hormone (sPTH), and osteocalcin (OCN) were prospectively assessed (baseline, T0, 3 months, T1, 6 months, T2). The primary endpoint was assessment of sBTM changes after denosumab; the secondary endpoints were disease-free survival (DFS) and sBTM correlation. Results: In 54 cases, sBTMs decreased during denosumab treatment except for sPTH. With a median follow-up of 59 months, 3-year DFS was 65% (%CI 52–79), with a significantly worse outcome for patients with high (≥500 UI/mL) s-CTX at baseline, as compared to low s-CTX (<500 UI/mL) (3-year DFS for high CTX 45% (95%CI 23–67) vs. 75% (95%CI 59–91) for low s-CTX. Higher median ALP and s-CTX were found for patients with tumor size ≥ 5 cm (p = 0.0512; p = 0.0589). Conclusion: Denosumab induces ALP/OCN and s-CTX reduction. High baseline s-CTX identifies a group of patients at higher risk of progression of the disease.

Giant cell tumour of bone in os sacrum of a prepubertal girl – Surgical and medical treatment with zoledronate and denosumab

“…A recent paper showed a significant decrease in ALP, CTX and osteocalcin after three months of denosumab treatment in adults with GCTB. Eight cases had unresectable GCTB and 43 underwent surgery after six months of treatment with denosumab, but there was no reporting of changes in BTMs with relapse of tumour despite a median follow-up time of 59 months ( Palmerini et al, 2022 ). As BSAP is readily available in many laboratories and cheap, we suggest BSAP to be a useful marker of tumour growth and activity.…”

Biological and Clinical Aspects of Metastatic Spinal Tumors

“…As a result of osteoblastic and osteoclastic transformations in bones, many chemical substances are released, which are termed bone turnover markers (BTMs) [ 136 ]. To detect BTMs, samples of blood serum or urine have to be tested.…”

Progress on Denosumab Use in Giant Cell Tumor of Bone: Dose and Duration of Therapy

“…Numerous basic and clinical studies have shown that denosumab is clinically beneficial for the treatment of advanced or metastatic GCTB [ 21 , 22 ]. However, various controversies regarding its use as a pre-operative adjuvant therapy prevail.…”