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.

Primary myelofibrosis (MF) is a severe chronic myeloproliferative neoplasm, progressing towards a terminal stage with insufficient haematopoiesis and osteosclerotic manifestations. Whilst densitometry studies have showed MF patients to have elevated bone mineral density, data on bone geometry and micro-structure assessed with non-invasive methods are lacking. We measured areal bone mineral density (aBMD) using dual-energy X-ray absorptiometry (DXA). Bone geometry, volumetric BMD, and micro-architecture were measured using high-resolution peripheral quantitative computed tomography (HR-pQCT). We compared the structural parameters of bones by comparing 18 patients with MF and healthy controls matched for age, sex, and height. Blood was analysed for biochemical markers of bone turnover in patients with MF. There were no significant differences in measurements of bone geometry, volumetric bone mineral density, and micro-structure between MF patients and matched controls. Estimated bone stiffness and bone strength were similar between MF patients and controls. The level of pro-collagen type 1 N-terminal pro-peptide (P1NP) was significantly increased in MF, which may indicate extensive collagen synthesis, one of the major diagnostic criteria in MF. We conclude that bone mineral density, geometry, and micro-architecture in this cohort of MF patients are comparable with those in healthy individuals.

Patients with the classical Philadelphia chromosome-negative chronic myeloproliferative neoplasms including essential thrombocythemia, polycythemia vera and primary myelofibrosis often suffer from comorbidities, in particular, cardiovascular diseases and thrombotic events. Apparently, there is also an increased risk of osteoporotic fractures among these patients. However, the true prevalence, mechanisms involved and therapeutic implications are not well described. In this review, we summarize what is currently known about possible associations between bone disease and chronic myeloproliferative neoplasms. Chronic inflammation has been suggested to explain the initiation of clonal development and progression in chronic myeloproliferative neoplasms. Decreased bone mineral density and enhanced fracture risk are well-known manifestations of many chronic systemic inflammatory diseases. As opposed to systemic mastocytosis (SM) where pathogenic mechanisms for bone manifestations probably involve effects of mast cell mediators on bone metabolism, the mechanisms responsible for increased fracture risk in other chronic myeloproliferative neoplasms are not known.

These results reveal no evidence of secondary osteoporosis among patients with ET or PV. The mechanism behind the increased fracture risk in ET or PV patients remains unknown.

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