Bone Mineral Density and Bone Microstructure in Patients with Haemophilia in Northern Germany: Preliminary Findings of a Single Centre Study

Scientific Research Question: Reduced bone mineral density (BMD) has been observed as a common co-morbidity in patients with haemophilia (PWH). The aim of our study was to describe the prevalence of reduced BMD in PWH in Northern Germany and to further determine the bone microstructure and the contributing factors to possible bone alterations.

Methodology: BMD, bone microstructure, laboratory parameters of bone metabolism, pain and orthopaedic joint status (OJS) were assessed routinely during check-ups. BMD was assessed by dual energy X-Ray absorptiometry (DXA) while bone microstructure was assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius and tibia. Furthermore, patients completed questionnaires on their activity and lifestyle after informed consent.

Findings: So far, data of 75 PWH (median age 33 years, range 18-77 years) could be retrospectively analysed, of whom 62 (83%) had haemophilia A and 13 (17%) haemophilia B. 54 PWH (72%) had severe, 7 (9%) moderate, 14 (19%) mild haemophilia, 7 patients (9%) had a previous inhibitor. Mean BMI was 25.7±3.9 kg/m², and mean vitamin D (25-hydroxyvitamin D) level was 16.9 ± 7.5 µg/l; 69 PWH (92%) had vitamin D deficiency (< 30 µg/l), 15 (20%) severe deficiency (< 10 µg/l). 12 PWH (16%) had osteoporosis, and 35 (46.1%) osteopenia, as defined by a T-score of ≤ −2.5 and < −1.0 (hip or spine), respectively. Among the 3 groups (normal BMD, osteopenia, osteoporosis), an association was found to BMI, OJS, physical function (Haemophilia Activities List, HAL) (in patients with osteoporosis lower BMI, p = 0.041, higher OJS, p < 0.01, lower HAL, p=0.012 was observed) while no differences were found regarding treatment regimen and exercise status. All patients with a previous inhibitor (n = 7) had osteopenia or osteoporosis. Of PWH, 39% had an impaired bone microstructure at the distal radius, and 45% of the tibia. In the radius 32% had isolated reduced cortical thickness (defined as < 70% of the age and gender matched mean), 3% a trabecular deficit and 7% a combined. In the tibia, 27% had an isolated trabecular, 7% a cortical and 12% a combined bone structural deficit. Regarding markers for bone metabolism, in PWH with osteoporosis a higher level of osteocalcin was observed (p=0.036).

Conclusions: Reduced BMD is a common finding in our population of PWH in northern Germany. An association to having a previous inhibitor, worse joint status and physical function was observed. Interestingly, bone structure deficits in radius are dominated by reduced cortical thickness whereas in the tibia a trabecular or combined structural deficit predominates, suggesting different pathophysiological mechanisms.

No conflict of interest has been declared by the author(s).