Nonremission and Recurrent Tumor-Induced Osteomalacia: A Retrospective Study

Abstract

Tumor‐induced osteomalacia (TIO) is a rare paraneoplastic syndrome. It is curable by excision of the causative tumor. However, a few cases may persist or relapse after tumor resection. We aimed to investigate the rate of these events and related factors. We retrospectively studied TIO patients treated with surgery in a tertiary hospital. TIO was established based on a pathologic examination or the reversion of hypophosphatemia. Refractory TIO patients consisted of those with nonremission or recurrent hypophosphatemia after surgery. A total of 230 patients were confirmed as having TIO. After primary surgery, 26 (11.3%) cases persisted, and 16 (7.0%) cases recurred. The overall refractory rate was 18.3%. The median time of recurrence was 33 months. Compared with patients in the recovery group, patients in the refractory group were more likely to be female (59.5% versus 41.0%, p = .029) and have a lower serum phosphate level (0.44 ± 0.13 versus 0.50 ± 0.11 mmol/L, p = .002). The refractory rate was lowest in head/neck tumors (7.5%) and highest in spine tumors (77.8%). Regarding the tissue involved of tumor location, the refractory rate was higher in tumors involving bone than tumors involving soft tissue (32.7% versus 7.0%, p < .001). The outcomes of malignant tumors were worse than those of benign tumors (p < .001): nonremission rate, 21.4% versus 9.7%; recurrence rate, 28.6% versus 6.5%. In the multivariate regression analysis, female sex, spine tumors, bone tissue‐involved tumors, malignancy, and low preoperation serum phosphorus levels were identified as risk factors for refractory outcomes. High preoperative fibroblast growth factor 23 (FGF23) levels were also associated with refractory after adjusting for involving tissue and tumor malignancy. In summary, we are the first to report the rate and clinical characteristics of refractory TIO in a large cohort. For patients with multiple risk factors, especially spine tumors, clinical practitioners should be aware of a poor surgical prognosis. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Burden of Disease in Patients With Tumor‐Induced Osteomalacia

“…(1,2) The largest cohort from a single center included 230 patients. (3) FGF23 excess leads to hypophosphatemia due to renal phosphate wasting and inappropriately normal or low 1.25 dihydroxy vitamin D. As a result, patients often present with a long history of musculoskeletal pain, fatigue, proximal muscle weakness, gait disturbance and multiple fractures. These debilitating symptoms are a consequence of severe hypophosphatemia and can lead to long-term disability and considerable morbidity.…”

“…Although complete tumor resection results in resolution of symptoms in most patients, (3) the diagnosis of TIO is commonly delayed due to its rarity and unspecific symptoms, and because tumor localization remains a challenging task. (4) In clinical practice TIO is largely known as a chronic condition that causes muscle quality deterioration and has a significant impact on quality of life.…”

A rare cause of atraumatic fractures: case series of four patients with tumor-induced osteomalacia

“…After the tumor has been localized, complete tumor resection with wide margins is recommended to decrease the likelihood of persistent or recurrent disease (Table 3). In a retrospective review of 230 patients with TIO, Li et al reported the incidence of persistent and recurrent TIO after the first surgery to be 11.3 and 7.0%, respectively, with the majority of cases due to suboptimal tumor resection [24]. In multivariable analysis, female sex, spine tumors, and bone tissue-involved tumors were identified as factors associated with refractory outcomes [24].…”

“…In a retrospective review of 230 patients with TIO, Li et al reported the incidence of persistent and recurrent TIO after the first surgery to be 11.3 and 7.0%, respectively, with the majority of cases due to suboptimal tumor resection [24]. In multivariable analysis, female sex, spine tumors, and bone tissue-involved tumors were identified as factors associated with refractory outcomes [24]. Additionally, each 0.31 mg/dL increase in the preoperative serum phosphorus level (range 0.59 to 2.1 mg/dL) was found to reduce the risk of refractoriness by more than 40% [24].…”

“…In multivariable analysis, female sex, spine tumors, and bone tissue-involved tumors were identified as factors associated with refractory outcomes [24]. Additionally, each 0.31 mg/dL increase in the preoperative serum phosphorus level (range 0.59 to 2.1 mg/dL) was found to reduce the risk of refractoriness by more than 40% [24]. Post-operative remineralization of the skeleton occurs immediately, but it may take at least one year for significant clinical improvement.…”