Study Rationale: Over half of all adults with thalassemia (Thal) have low bone mass, bone pain and are at significant risk for fracture. Current clinical strategies are ineffective at improving bone health as even optimally transfused and chelated patients and those with normal endocrine function continue to have bone deficits. Despite severely low bone mineral density (BMD) Z-scores, bisphosphonate therapies are contra-indicated in some Thal given their young age and kidney dysfunction. When bisphosphonates are prescribed, the costly intervention manages the problem after osteoporosis has developed. Non-invasive strategies that address inadequate bone formation, the root of the issue in patients with Thal, are needed. Exercise has been shown in non-Thal populations to increase bone strength, enhance muscle mass, improve glucose tolerance, and reduce pain. In fact, some have purported that exercise is more effective and safer than many drugs available for chronic diseases. Given the significant bone deficits observed, and the relative inactivity observed in many, a focused, personalized exercise regime has the potential to not only improve bone health but may also have positive effects on bone pain, reduce fatigue and improve overall quality of life in patients with Thal.

Study Objectives

  • To determine the change in body composition in patients with Thal (15 – 40 years) who participate in a 36-week, weight bearing exercise intervention (30 min/day; 5x/week) compared to usual activity.

  • To determine the change in upper and lower body muscle function in patients with Thal who participate in a 36-week, weight bearing exercise intervention compared to usual activity.

  • To determine the change in total body, spine, hip and radius BMD by DXA in patients with Thal and low bone mass who participate in a 36-week, weight bearing exercise intervention compared to usual activity.

  • To determine the change in bone strength and geometry by pQCT in the tibia and radius in patients with Thal who participate in a 36-week, weight bearing exercise intervention compared to usual activity.

Study Design: A minimum of 20 subjects with Thal are invited to participate in a ‘delayed start’ study design, where they will serve as their own controls. The change in study variables (body composition, muscle function, QOL, pain, BMD by DXA and pQCT) will be monitored for 12 weeks (Usual Activity) after which subjects are enrolled into the Exercise Intervention (36 weeks) comprised of aerobic (minimum of 3x/week, 30 min/day) plus strength training exercises (minimum of 2x/week, 30 min/day). The exercise intervention is a home-based program, adaptable to the subjects' schedule and level of fitness, designed to comply with the CDC recommendations for physical activity and scalable to increase intensity as fitness level improves. A wearable activity monitor (FitBit) is provided to each subject at the start of the intervention with the dual purpose of providing positive feedback to the subjects and a direct assessment of activity to the investigators. Adherence will also be assessed via daily self-reported electronic survey. Study visits will be conducted at 0, 12, 18, 24 and 36 weeks, with the following assessments: DXA (Horizon A, Hologic) to determine BMD, lean, total and visceral fat mass; peripheral quantitative computed tomography (pQCT, XCT2000, Stratec) for volumetric BMD at the radius and tibia; hand grip strength for upper body muscle function, sit-to-stand and vertical jump for lower body muscle power, and the 6-minute walk test as a marker of endurance. Subjects will also complete the SF36 health questionnaire and the brief pain inventory at each visit.

Eligibility Criteria: Subjects will be included if they have Thal (any genotype, regardless of transfusion dependency), are aged 15 - 40 years, and have a BMD Z-score at any skeletal site < -1.0. Subjects are excluded if they are pregnant, routinely exercise for more than 45 min/day, hypogonadal, on hormone replacement therapy for less than 6 months, have evidence of cardiovascular disease or severe cardiac iron overload, had a fracture within the last 6 months, or have used a bisphosphonate medication in the last 2 years.

Significance: If effective, this simple, non-invasive, cost-effective, easy to implement exercise therapy could be expanded broadly to have positive effects not only on bone health but also quality of life for patients with Thal at significant risk for fracture.

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2025
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