Chronic myeloproliferative neoplasms and risk of osteoporotic fractures; a nationwide population‐based cohort study

Abstract

SummaryPatients with systemic mastocytosis have an increased risk of osteoporosis, however, the risk of osteoporotic fractures among the classic chronic myeloproliferative neoplasms (CMPN), including essential thrombocythaemia (ET), polycythaemia vera (PV) and chronic myeloid leukaemia (CML), is unknown. We conducted a population-based cohort study to determine the risk of osteoporotic fractures among three cohorts of patients with newly diagnosed ET, PV, and CML. Patients were identified in medical registers including all Danish hospitals during 1980-2010 and were followed until first osteoporotic fracture. Fracture risk was compared to cohorts from the general population matched on age, sex and calendar year. We followed 7595 CMPN patients and 338 974 comparison cohort members. We found that the risk of femoral fracture after 5 years was consistently higher than the general population, being 3Á01% (95% confidence interval (CI): 2Á20-4Á10), 4Á74% (95%CI: 4Á06-5Á52) and 4Á64% (95%CI: 3Á29-6Á53) among ET, PV, and CML patients respectively. Adjusted hazard ratio for femoral fracture was increased 1Á19-fold (95% CI: 0Á94-1Á51) for ET patients, 1Á82-fold (95% CI: 1Á62-2Á04) for PV patients, and 2Á67-fold (95% CI: 1Á97-3Á62) for CML patients. We conclude that CMPN patients are at higher risk of osteoporotic fractures than the general population.

Polycythemia is associated with bone loss and reduced osteoblast activity in mice

“…Using micro-CT, we observed similar bone loss in both mice suggesting that chronic polycythemia affects bone remodeling and can be a risk factor for osteoporosis. In accordance to our animal data, a clinical study by Farmer et al showed that the risk of femoral fractures is increased by 4.74 % in patients 5 years after diagnosis of polycythemia vera compared to the general population [11]. Increased fragility was also observed among patients with other myeloproliferative syndromes, which are also characterized by hematopoietic expansion.…”

“…In animals, a decrease in bone mass was observed after bleeding, phenylhydrazine-induced hemolysis, or inflammation induced anemia [10]. Beyond anemias, a recent report found increased fragility in patients suffering from disorders characterized by hematopoietic expansion, such as polycythemia vera (PV) and other chronic myeloproliferating syndromes [11]. However, the presence of osteoporosis in these patients has not yet systematically been studied.…”

The Many Facets of Erythropoietin Physiologic and Metabolic Response

“…EPO administration has also demonstrated the capacity to affect bone remodeling, but in two disparate ways: accelerate bone healing in animal models of bone fracture, and cause bone loss in healthy animals responding with increased erythropoiesis. More studies in understanding the role of EPO in bone in specific pathological conditions are warranted as patients with diseases associated with high circulating EPO such as thalassemia (Vichinsky, 1998), sickle cell disease (Sarrai et al, 2007), and polycythemia vera (Farmer et al, 2013) have debilitating bone conditions.…”

Perspectives on the impact of JAK-inhibitor therapy upon inflammation-mediated comorbidities in myelofibrosis and related neoplasms

“…Similarly, abnormal blood glucose profiles (glycated hemoglobin) in patients with type 2 DM, a chronic inflammatory metabolic syndrome, may likely improve as a result of an improved glucose homeostasis consequent to a decrease in elevated levels of inflammatory cytokines and, accordingly, may lead to amelioration of inflammationmediated insulin resistance. Combination therapy may likely improve osteopenia and, accordingly, decrease the risk of fractures, which has recently been documented in MPNs [101]. Furthermore, in JAK2 V617-positive patients, combination therapy may be associated with a more rapid reduction in JAK2 V617F allele burden and therefore decrease the risk of thrombosis and disease progression, as the JAK2 V617F mutation is suggested to promote thrombosis and induce genetic instability with an inherent increased risk of subclone formation and development of resistance to therapy, respectively.…”