Characterising Pain, Quality of Life, Body Composition, Arterial Stiffness, Muscle Function, Bone Density and Geometry in Adult Persons With Hereditary Hypophosphatemia and Healthy Controls
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 92
- 试验地点
- 1
- 主要终点
- Health-related quality of life: SF36v2
研究概览
简要总结
Hereditary hypophosphatemia (XLH) is a rare, inherited disease. Loss-of-function mutation in the phosphate regulating gene with homologies to endopeptidases on the X-chromosome (PHEX) results in excess fibroblast growth factor 23 (FGF23) production and manifests as rickets in children and osteomalacia in adults.
This study aims to characterize and measure pain, quality of life, muscle function, body composition, arterial stiffness, bone mineral density, geometry and microarchitecture in patients with XLH compared to age and gender-matched controls.
详细描述
Hereditary hypophosphatemia (XLH) is a rare, inherited disease. Loss-of-function mutation in PHEX results in excess fibroblast growth factor 23 (FGF23) production and manifests as rickets in children and osteomalacia in adults. FGF23 is a hormone that reduces renal phosphate reabsorption, decreases renal 1α-hydroxylase activity and increases renal 24-hydroxylase activity. As a consequence, individuals with XLH display hypophosphatemia and inadequate levels of 1,25(OH)2D (1). Therefore, conventional medical treatment of XLH aims to replace the loss with oral phosphate and activated vitamin D analogues.
The pain experienced by patients with hypophosphatemic rickets is not well characterized and needs to be addressed in order to establish the most optimal pain management in patients with XLH. The causes of pain experienced by patients with XLH are numerous: osteomalacia, enthesopathy, muscular pain, lower limb deformities, secondary arthrosis, nerve compression, and dental abscesses (3).
Quality of life (QoL) in patients with XLH is only briefly studied (4, 5). A French study found significantly decreased QoL among adult patients with XLH compared to patients with axial spondylarthritis. Especially enthesopathies were associated with a decreased QoL (4).
Increased blood levels of FGF23 are not associated with increased risk of cardiovascular disease in itself (6-8). However, conventional therapy for patients with XLH may increase their cardiovascular risk since complications to the therapy such as nephrocalcinosis and hyperparathyroidism are associated with increased cardiovascular risk. Arterial stiffness may be a valuable marker of increased cardiovascular risk as it has been able to predict cardiovascular disease and mortality in different populations (10, 11). If conventional therapy increases the risk of cardiovascular morbidity and mortality, arterial stiffness may be increased among patients with XLH which may depend on treatment status (i.e., currently treated, currently non-treated, accumulated (years of) treatment and treatment naïve).
Patients with XLH often complain about muscle fatigue and exhaustion. Muscle function in XLH is thought to be compromised by chronic hypophosphatemia, but the effect of XLH on muscle function has only been briefly evaluated (12, 13).
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Understand oral and written Danish
- •Able to consent
- •For XLH only:
- •genetically verified XLH by detection of a disease-causing mutation in PHEX or a positive family history of X-linked hypophosphatemia.
- •biochemically verified hereditary hypophosphatemia: serum PO4 below normal range and low TmPO4/GFR, and/or elevated serum FGF23 and a history of childhood rickets or spontaneous endodontic abscesses to exclude acquired hypophosphatemia, e.g., tumor-induced osteomalacia.
排除标准
- •P-25OHD < 25 mmol/L*
- •Severe co-morbidities, which in the opinion of the investigator may have major impact on study outcomes. This may include, but is not limited to o poorly controlled hyperthyroidism o Paget disease
- •o type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus
- •o severe and chronic cardiac, liver, or renal disease
- •o Cushing syndrome
- •o Rheumatoid arthritis
- •o Active pancreatitis
- •o Malnutrition
- •o Recent prolonged immobility*
- •o Active malignancy (including myeloma)
- •Treatment with
- •o Burosumab
- •Beta-blockers
- •Oral steroids
- •For controls only:
- •disturbances in the calcium or phosphate homeostasis
- •participants with low 25OHD levels or recent immobility may be re-screened for participations 6 months after this has been corrected
结局指标
主要结局
Health-related quality of life: SF36v2
时间窗: Day 1
Assessed by questionnaire (SF36v2) on a scale from 1 to 5. Higher scores meaning a worse outcome.
Vertebral Fracture Assessment
时间窗: Day 2
Assessed by DXA
Mineralization lag time
时间窗: 14 days
Histomorphometry on bone biopsy
Volumetric bone mineral density
时间窗: Day 1
Assessed by HRpQCT of distal tibia, distal radius, and bone biopsy
Mineralization rate
时间窗: 14 days
Histomorphometry on bone biopsy
Osteoid volume
时间窗: 14 days
Osteoid volume in trabecular and compact bone assessed by histomorphometry on bone biopsy
Quality of life in patients with bone-specific pain
时间窗: Day 1
Assessed by questionnaire (FACT-BP) on a scale from 0 to 4. Higher scores mean a worse outcome.
Maximal force production
时间窗: Day 2
Handgrip strength, elbow and knee flexion and extension assessed by dynamometer chair (Good Strength; Metitur Ltd, Finland).
Repeated weight lifting
时间窗: Day 2
Measures the time for ten consecutive weight lifts.
Arterial stiffness
时间窗: 24 hours
Assessed by tonometry using Arteriograph24
Repeated chair rising
时间窗: Day 2
Measures the time for ten consecutive chair rises.
Bone microarchitecture
时间窗: Day 1
Assessed by HRpQCT of distal tibia, distal radius, and bone biopsy
Neuropathic pain: questionnaire (painDETECT)
时间窗: Day 1
Assessed by questionnaire (painDETECT) on a scale from 0 to 10. 0 meaning no pain, 10 meaning worst pain ever.
General pain: Brief Pain Inventory
时间窗: Day 1
Assessed by questionnaire (Brief Pain Inventory) on a scale from 0 to 10. 0 meaning no pain, 10 meaning worst pain ever.
Timed Up and Go
时间窗: Day 2
Measures the time to stand up, walk three metres in a straight line, and immediately return to the chair.
Body composition
时间窗: Day 2
Assessed by DXA
Bone geometry
时间窗: Day 1
Assessed by HRpQCT of distal tibia, distal radius, and bone biopsy
Osteoid surface covering
时间窗: 14 days
Osteoid surface covering in trabecular and compact bone assessed by histomorphometry on bone biopsy
PPT
时间窗: Day 2
Pressure pain threshold assessed by pressure algometry
Osteoid thickness
时间窗: 14 days
Osteoid thickness in trabecular and compact bone assessed by histomorphometry on bone biopsy
Percentage of surface covered by osteoblasts
时间窗: 14 days
Assessed by histomorphometry on bone biopsy
Lacunar concentration of mineralization inhibitors
时间窗: 14 days
Assessed by nano-scale on bone biopsy
Systolic and diastolic blood pressure
时间窗: 24 hours
24 hour blood pressure of the upper right arm
Pulse wave velocity
时间窗: 45 minutes
Assessed by tonometry using SphygmoCor system
Maximum strength
时间窗: Day 2
Handgrip strength, elbow and knee flexion and extension assessed by dynamometer chair (Good Strength; Metitur Ltd, Finland).
6-minutes' walk test
时间窗: Day 1
Measures the distance walked in 6 minutes.
Estimated bone strength
时间窗: Day 1
Assessed by HRpQCT of distal tibia, distal radius, and bone biopsy
Percentage of surface covered by osteoclasts
时间窗: 14 days
Assessed by histomorphometry on bone biopsy
次要结局
- Anxiety(Day 1)
- Depression(Day 1)
- Catastrophic thinking(Day 1)