Baseline Osteopenia and Osteoporosis in Untreated Non-Hodgkin’s Lymphoma Patients.
Authors: Thompson Michael A. , Huen Auris , Ayers Gregory D. , Toth Bela B. , Sellin Rena V. , Hoff Ana O. , Murphy William A. , Hagemeister F.B. 
Published: April 2020

Abstract
BACKGROUND: Lymphoma treatment with alkylating agents and steroids can cause premature osteoporosis, increasing the risk of vertebral and hip fracture. Mechanisms of bone loss may include local microenvironment lymphoma-related cytokine activity, steroid-mediated bone loss, and hypogonadism from chemotherapy. The bisphosphonate pamidronate every three months has been found to reduce bone loss and the risk of new vertebral fractures in lymphoma patients receiving chemotherapy; however, the more potent bisphosphonate, zoledronic acid, has not been evaluated in this patient population. We are conducting a randomized study of zoledronic acid in untreated non-Hodgkin’s lymphoma (NHL) patients to study chemotherapy induced bone loss and improve NHL survivorship. While this trial is still accruing patients, we report the abnormal baseline bone mineral density (BMD) and endocrine characteristics found in patients screened for this study.
METHODS: We report the preliminary baseline endocrine characteristics for this ongoing bone health research study. Untreated NHL patients were screened for BMD and endocrine studies including vitamin D levels, testosterone, and bone turnover markers. Patients on the study were stratified as male, female (pre-menopausal), and female (post-menopausal). Exclusion criteria included bone fractures, BMD T-scores worse than −2.0, creatinine clearance less than 60 mL/min, dental problems, and prior steroid or bisphosphonate use. Patients accrued to the study are randomized to receive either: 1) oral calcium and vitamin D (Ca+D) or 2) Ca+D and 4 mg zoledronic acid IV at baseline and at 6 months.
RESULTS: Patient characteristics included: 49 male, 35 female (10 pre-menopausal), median age 61 (range: 18–87). Of 84 patients screened for BMD to date, patients had the following abnormalities: 12/84 (14%) had osteoporosis and 47/84 (56%) had osteopenia or osteoporosis. Of 20 patients who consented to the trial and who were evaluated with additional studies, 10 were excluded due to the following: 3/20 hypovitaminosis D, 1/20 with prior steroid use, 1/20 low testosterone, 1/20 prior HRT, 1/20 with bone disease, 2/20 required dental extractions, and 1/20 treatment changed to chemotherapy without steroids. Patients with osteoporosis or T score worse than −2.0 were evaluated by their primary oncologist for treatment with bisphosphonates. Patients with other abnormal studies were further evaluated and treated by specialists in endocrinology and dentistry.
CONCLUSIONS: Baseline testing of BMD and endocrine studies revealed osteopenia or osteoporosis in 56% of untreated NHL patients. Hypovitaminosis D or low testosterone was found in a smaller number of tested patients. While these patients were excluded from the remainder of the study and referred for further evaluation, patients should benefit from having these underlying problems addressed. Our ongoing clinical trial will address the potential role of zoledronic acid in preserving bone density for survivors of NHL. This trial was funded by Novartis.
ClinicalTrials.gov Identifier: NCT00352846.