RecruitingACTRN12621001397808

The Haemophilia Osteoporosis Registry (THOR): Identifying Mechanisms of Bone Loss in Haemophilia

Sponsor

Monash University

Enrollment

176 participants

Start Date

Jun 9, 2022

Study Type

Observational

Conditions

Haemophilia A Sarcopenia Osteoporosis Osteoarthritis

Summary

Treatment for haemophilia has improved immensely over the past 30 years which has increased the life expectancy in these patients. As such, comorbidities of ageing and their impact is now an area of importance – in particular musculoskeletal health. Reports have shown that fracture incidence is higher in patients with haemophilia, with disease severity effecting fracture risk. Currently the underlying mechanisms of increased fracture risk in patients with haemophilia is unknown, or what age the bone loss begins and whether or not this is different to the general population. Majority of existing studies have reported low areal bone mineral density (aBMD) measured with dual energy x-ray absorptiometry (DXA), however, other components of bone strength may be compromised, and may also contribute to the increased fracture risk. For example, the separate bone compartments (cortical vs trabecular), bone geometry (shape and size), microarchitecture (organisation of trabecular bone) and bone strength (buckling vs strain). With the advancements in bone imaging technology, these other components of bone strength can now be measured using cutting-edge high-resolution peripheral quantitative computed tomography (HRpQCT). Currently there are no guidelines on bone density screening or osteoporosis treatment for patients with haemophilia. As such, it is unknown when the best “window or age” for bone density screening would be most effective to prevent fracture. The findings from this study will indicate at which age bone density screening will be most beneficial for patients with haemophilia A. Therefore, The Haemophilia Osteoporosis Registry (THOR) is timely as it has been empirically designed and powered to identify the mechanisms of bone loss in patients with haemophilia.

Eligibility

Sex: MalesMin Age: 18 Yearss

Inclusion Criteria12

Eligibility for inclusion as a participant in this study will require a potential participant to satisfy all of the following eligibility criteria:
Aged 18 years or older
Male
Body weight less than 160 kg (maximum rating of imaging machines).
At least one side of the body must be free from any metal, or other material in limbs or surrounding locations, that could interfere with imaging.
Fluent in written and spoken English, has capacity to provide informed consent and can communicate effectively with researchers. A legally acceptable representative and/or impartial witness fluent in written and spoken English and the participant’s first/fluent language acting as translator will also be acceptable, providing they are able to attend all scheduled sessions with the participant.
Patients with haemophilia recruited for the study should also satisfy the additional criterion below:
Previously diagnosed with moderate to severe haemophilia A
Participants in the control group should also satisfy the additional criteria below:
Be in good health without any major medical co-morbidities (diabetes, chronic kidney disease and recent cardiovascular events – stroke, myocardial infarction or heart attack)
No other medical condition that in the opinion of the investigators may deem inclusion unsafe or inappropriate (e.g., recent exposure to nuclear medicine; conditions that may reduce ability to remain supine during DXA (e.g., vertigo); conditions that may reduce ability to remain still during scans (e.g. Parkinson’s disease, motor-neuron disease).
Not be on medications that targets bone health e.g., Alendronate (Fosamax), Risedronate (Actonel), Ibandronate (Boniva), Zoledronate (Aclasta), Denosumab (Prolia), Teriparatide (Forteo) and Romosozumab (Evenity).

Exclusion Criteria4

For all participants:
Have other medical condition that in the opinion of the investigators may deem inclusion unsafe or inappropriate (e.g., recent exposure to nuclear medicine; conditions that may reduce ability to remain supine during DXA (e.g., vertigo); conditions that may reduce ability to remain still during scans (e.g. Parkinson’s disease, motor-neuron disease).
Control participants:
On medications that targets bone health e.g., Alendronate (Fosamax), Risedronate (Actonel), Ibandronate (Boniva), Zoledronate (Aclasta), Denosumab (Prolia), Teriparatide (Forteo) and Romosozumab (Evenity).

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Interventions

This is a prospective longitudinal observational study, recruiting men with haemophilia A and age-matched controls residing in Victoria, Australia, with a total of 176 participants. Stratified sampling by age will be used to ensure equal distribution across the four age-bands, namely 18-30, 31-40, 41-50, 51+ years. Recruitment will include: patients with haemophilia A will be approached during clinical consultations (in person or via telehealth) at Alfred Health. Each patient who is approached to join the study will be recorded in the Log Book. If patients consent to passing on their contact details, the consultant will refer the patients to the team at Monash Medical Centre to discuss the study in further detail. Potential participants will undergo screening against criteria to determine their eligibility for participation. The age-matched controls will be recruited through: - Posters displayed throughout Monash Medical Centre and Monash University Clayton Campus, and; - Email lists, newsletters, social media, recruitment registry, community organisations, local social and sports clubs will also be employed to advertise recruitment Participants will come into Monash Medical Centre for a study visit at baseline and follow-up 1, with an interval of 12 months between study visits. Data collected will include: - Questionnaires: general demographics, medical history, including medication use and co-morbidities at baseline (General Questionnaire); health changes during the study will be collected at follow-up (General Medical Hx Update); Patient Reported Outcomes Burdens and Experiences (PROBE) questionnaire (containing the EQ-5D-5L and VAS); Bone-specific Physical Activity Questionnaire (BPAQ or BSPA in REDCap); International Physical Activity Questionnaire (IPAQ); Gilbert Joint Health Score questionnaire (Gilbert Score). - Anthropometry: height, weight and sidedness - Bloods: fasting blood samples will be collected to measure procollagen type 1 N propeptide (P1NP), C-terminal telopeptide of type 1 collagen (CTX), calcium, phosphate, vitamin D, and liver function tests (bilirubin, albumin, GGT, ALP, AST, ALT). - Bone health: dual energy x-ray absorptiometry (DXA) and high resolution peripheral quantitative computed tomography (HR-pQCT) - Joint health: HR-pQCT will scan the ankle and knee joints - Body composition: DXA - Muscle strength: hand grip strength and jumping mechanography These will all be collected at both study visits by the research team (including research assistant, Research Fellow, Students (ie PhD, Honours, Medical students). The anticipated duration of each study visit is 1.5hrs.