The Effect of Biochemical Remission on Bone Metabolism in Cushing's Syndrome: A 2-Year Follow-Up Study

Abstract

Endogenous Cushing's syndrome (CS) is a rare cause of secondary osteoporosis. The long‐term consequences for bone metabolism after successful surgical treatment remain largely unknown. We assessed bone mineral density and fracture rates in 89 patients with confirmed Cushing's syndrome at the time of diagnosis and 2 years after successful tumor resection. We determined five bone turnover markers at the time of diagnosis, 1 and 2 years postoperatively. The bone turnover markers osteocalcin, intact procollagen‐IN‐propeptide (PINP), alkaline bone phosphatase, CTX‐I, and TrAcP 5b were measured in plasma or serum by chemiluminescent immunoassays. For comparison, 71 sex‐, age‐, and body mass index (BMI)‐matched patients in whom Cushing's syndrome had been excluded were studied. None of the patients received specific osteoanabolic treatment. At time of diagnosis, 69% of the patients had low bone mass (mean T‐score = −1.4 ± 1.1). Two years after successful surgery, the T‐score had improved in 78% of patients (mean T‐score 2 years postoperatively −1.0 ± 0.9). The bone formation markers osteocalcin and intact PINP were significantly decreased at time of diagnosis (p ≤ 0.001 and p = 0.03, respectively), and the bone resorption marker CTX‐I and TrAcP 5b increased. Postoperatively, the bone formation markers showed a three‐ to fourfold increase 1 year postoperatively, with a moderate decline thereafter. The bone resorption markers showed a similar but less pronounced course. This study shows that the phase immediately after surgical remission from endogenous CS is characterized by a high rate of bone turnover resulting in a striking net increase in bone mineral density in the majority of patients. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Metformin and Bone Metabolism in Endogenous Glucocorticoid Excess: An Exploratory Study

“…In CS-MET group, 9 out of 10 patients continued metformin therapy until one-year follow-up. For the comparison of bone remodeling markers, a previously described registry control group of patients in whom CS was excluded (NO-CS group, n=95) was used ( 14 ). The German Cushing’s Registry (NeoExNet, No.…”

“…This cohort study was performed as part of the German Cushing's Registry. General characteristics of the registry have been described in detail previously (12)(13)(14). We screened the prospective registry cohort consisting of 96 patients with endogenous CS for metformin intake at the time of diagnosis.…”

Cortisol and Phosphate Homeostasis: Cushing’s Syndrome Is Associated With Reversible Hypophosphatemia

“…Cushing’s syndrome (CS) results from chronic exposure to either endogenous or exogenous excess of cortisol ( 1 ). A well-known complication of hypercortisolism in CS is glucocorticoid-induced osteoporosis (GOP) ( 2 , 3 ). GOP is thought to be the result of a combination of decreased intestinal calcium absorption and renal calcium resorption, increased bone resorption, decreased bone formation and muscle wasting.…”

“…GOP is thought to be the result of a combination of decreased intestinal calcium absorption and renal calcium resorption, increased bone resorption, decreased bone formation and muscle wasting. Consequently, biochemical remission of Cushing’s syndrome results in an increase in bone mineral density ( 3 ). Recently, it has been suggested that treatment with glucocorticoids could also affect phosphate homeostasis and even induce hypophosphatemia due to increased urinary phosphate excretion ( 4 , 5 ).…”

The Effect of Biochemical Remission on Bone Metabolism in Cushing's Syndrome: A 2-Year Follow-Up Study

“…First and foremost, we appreciate the great interest of Dutta and colleagues in our work. (1) We provide a few comments and clarifications.…”