Enhancing Skeletal Adaptation to Exercise by Attenuating the Acute Disruption of Calcium Homeostasis During Exercise
概览
- 阶段
- 不适用
- 干预措施
- Endurance exercise intervention
- 疾病 / 适应症
- Exercise
- 发起方
- VA Office of Research and Development
- 入组人数
- 18
- 试验地点
- 2
- 主要终点
- Procollagen 1 intact N-terminal propeptide (P1NP)
- 状态
- 已完成
- 最后更新
- 26天前
概览
简要总结
Exercise is essential for building and maintaining bone mass and strength, but current exercise recommendations for how to achieve this lack detail on the optimal exercise prescription. Recent studies found that blood calcium level decreases during exercise, and that calcium is mobilized from bone to slow the decline. If this occurs repeatedly during exercise training, it could diminish the potential benefits of exercise to improve bone health. The proposed study will determine whether further research on pre-exercise supplemental calcium to minimize the decline in blood calcium level during exercise is warranted. This research is important for Veterans because they are at increased risk of hip fracture when compared with non-Veterans. Further, because osteoporosis in men is under-recognized and under-treated, providing male (and female) Veterans with more specific exercise and nutrition guidelines has the potential to enhance bone health, reduce fracture risk, and improve quality of life.
详细描述
Exercise is essential for building and maintaining bone mass and strength, but recent work has raised the possibility that current exercise recommendations for bone health may not be appropriate. There is strong evidence that a single bout of vigorous exercise has an acute catabolic effect in bone (i.e., increased resorption) that lasts several hours. This is mediated by a decrease in serum calcium (Ca) during exercise, which stimulates parathyroid hormone (PTH) secretion. PTH then activates bone resorption to mobilize Ca from bone, presumably to prevent the decrease in serum Ca from progressing to a harmful level. This cascade of events can be markedly attenuated by minimizing the decline in serum Ca during exercise via either intravenous or oral Ca administration. The timing of Ca supplementation relative to exercise is likely important, because it must be available for gut absorption during exercise. Interestingly, repeated pharmacologic stimulation of the PTH receptor with PTH analogs (teriparatide, abaloparatide) has anabolic effects on bone, suggesting that repeated exercise-induced increases in PTH could have a chronic anabolic skeletal effect, in addition to the acute catabolic effect, which may be apparent only after repeated exercise sessions. If this is the case, suppressing the PTH response with pre-exercise Ca supplementation may not be appropriate. In this context, this proof-of-concept study will include a short exercise intervention consisting of treadmill exercise at 70% to 80% of maximal heart rate, 60 minutes per day, 4 days per week, for 4 weeks. Serum markers of bone formation and resorption will be measured before, during, and for 24 hours after the 1st, 8th, and 16th exercise sessions to address two questions: 1) Does the acute catabolic response of bone to a single bout of exercise continue to occur with repeated exercise sessions (i.e., exercise training)? 2) Does exercise training also generate an anabolic PTH-mediated bone response, similar to the anabolic response to PTH analog therapy? If the answers to questions 1 and 2 are YES (persistent catabolic signal) and NO (lack of anabolic signal), this will support the need for the randomized controlled trial (RCT), which will evaluate whether taking Ca before exercise to attenuate the acute catabolic response improves skeletal adaptations to exercise training. The overarching goal is to improve the currently imprecise recommendations for exercise to improve and maintain bone health. This research is of high relevance to Veterans, who are at increased risk of hip fracture when compared with non-Veterans. Further, because osteoporosis in men is under-recognized, under-diagnosed, and under-treated, providing male Veterans with an effective non-pharmacologic therapeutic option to reduce fracture risk may help close this treatment gap. The potential impact of this research also extends beyond Veterans. It could lead to reduced risk of exercise-related bone injury (i.e., stress fractures) in active duty military personnel and athletes and to improved bone health in the general population.
研究者
入排标准
入选标准
- •Female and male Veterans aged 25 to 45 y and 55 to 75 y will be enrolled. Eligible volunteers will be normally active (e.g., recreational cycling or walking) but will not participate in regular moderate-to-vigorous exercise. Women will be premenopausal with regular menstrual cycles or postmenopausal, defined as absence of menses for at least 12 mo or, in those who underwent a hysterectomy, a serum follicle stimulating hormone (FSH) \>30 mIU/mL.
排除标准
- •Initiation or change in dose in the past 6 months of medications that affect bone metabolism
- •e.g., osteoporosis medications, thiazide/loop diuretics, systemic glucocorticoids
- •BMD T-score \<-2.5 at the total hip, femoral neck, or lumbar spine
- •Impaired renal function, defined as an estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73m2
- •Abnormal alkaline phosphatase
- •Untreated thyroid dysfunction, defined as an ultrasensitive thyroid stimulating hormone (TSH) \<0.5 or \>5.0 mU/L
- •Serum Ca \<8.5 or \>10.3 mg/dL
- •Serum 25(OH)D \<20 ng/mL
- •Uncontrolled hypertension (resting systolic blood pressure (BP) \>150 mmHg or diastolic BP \>90 mmHg)
- •Type 1 diabetes
研究组 & 干预措施
Exercise
All participants engage in exercise training
干预措施: Endurance exercise intervention
结局指标
主要结局
Procollagen 1 intact N-terminal propeptide (P1NP)
时间窗: The primary outcome for Aim 2 is the change in the pre-exercise P1NP (15 minutes before the start of exercise) from the 1st to the 16th exercise session.
P1NP is a marker of bone formation. An increase in P1NP from before to after an exercise intervention is evidence of an anabolic response of bone.
C-terminal peptide of type 1 collagen (CTX)
时间窗: The primary outcome for Aim 1 is the change in CTX (dCTX) from before exercise to the peak during 4 hours of recovery measured during the 1st, 8th, and 16th exercise sessions.
CTX is a marker of bone resorption. An increase in CTX in response to exercise is evidence of an acute catabolic response of bone.
Change in C-terminal Peptide of Type 1 Collagen (CTX)
时间窗: The primary outcome for Aim 1 is the change in CTX from immediately before exercise to 60 minutes after exercise during the 1st, 8th, and 16th exercise bout. Results are for each exercise bout and for the average of all the bouts combined.
CTX is a marker of bone resorption. An increase in CTX in response to exercise is evidence of an acute catabolic response of bone.
Change in Procollagen 1 Intact N-terminal Propeptide (P1NP)
时间窗: The primary outcome for Aim 2 is the change in the pre-exercise P1NP (15 minutes before exercise) between the 1st and the 16th exercise bout (comparison of 2 time points).
P1NP is a marker of bone formation. An increase in P1NP from before to after an exercise intervention is evidence of an anabolic response of bone.
次要结局
- Serum ionized Ca (iCa)(Serum iCa is measured before (-15, 0 minutes), during (15, 30, 45, 60 minutes), and after (15, 30, 60, 120, 180, 240 minutes, 24 hours) the 1st, 8th, and 16th exercise sessions)
- P1NP(Serum P1NP is measured before (-15, 0 minutes), during (15, 30, 45, 60 minutes), and after (15, 30, 60, 120, 180, 240 minutes, 24 hours) the 1st, 8th, and 16th exercise sessions)
- Urinary calcium excretion (uCa)(Urinary Ca excretion is measured over the 4 hours of recovery after the 1st, 8th, and 16th exercise sessions)
- Serum parathyroid hormone (PTH)(Serum PTH is measured before (-15, 0 minutes), during (15, 30, 45, 60 minutes), and after (15, 30, 60, 120, 180, 240 minutes, 24 hours) the 1st, 8th, and 16th exercise sessions)
- Serum phosphorus (PO4)(Serum PO4 is measured before (-15, 0 minutes), during (15, 30, 45, 60 minutes), and after (15, 30, 60, 120, 180, 240 minutes, 24 hours) the 1st, 8th, and 16th exercise sessions)
- Hematocrit (Hct)(Hct is measured before (-15, 0 minutes), during (15, 30, 45, 60 minutes), and after (15, 30, 60, 120, 180, 240 minutes, 24 hours) the 1st, 8th, and 16th exercise sessions)
- Serum total Ca (tCa)(Serum tCa is measured before (-15, 0 minutes), during (15, 30, 45, 60 minutes), and after (15, 30, 60, 120, 180, 240 minutes, 24 hours) the 1st, 8th, and 16th exercise sessions)
- Hemoglobin (Hgb)(Hgb is measured before (-15, 0 minutes), during (15, 30, 45, 60 minutes), and after (15, 30, 60, 120, 180, 240 minutes, 24 hours) the 1st, 8th, and 16th exercise sessions)
- Change in P1NP During Exercise(Change in serum P1NP is measured from before to immediately after the 60 minutes of exercise during the 1st, 8th, and 16th exercise bout. The average change across all exercise bouts is also included.)
- Urinary Calcium Excretion (uCa)(Urinary Ca excretion is measured over the 4 hours of recovery after exercise. Results are presented for the 1st, 8th, and 16th exercise bout individually and for the average excretion across all 3 collections.)
- Change in Serum Ionized Ca (iCa)(Serum iCa is measured before and 15 minutes after the 60 minutes of exercise during the 1st, 8th, and 16th exercise bout. Average change across all three exercise collection bouts is also provided.)
- Change in Serum Total Ca (tCa)(Change in serum tCa is measured before and 15 minutes after the 60 minute exercise bout during the 1st, 8th, and 16th exercise bouts. Average change across all 3 collection bouts is also included.)
- Change in Serum Parathyroid Hormone (PTH)(Serum PTH is measured before and 15 minutes after the 60 minute exercise bout. Results are presented for the 1st, 8th, and 16th exercise bouts individually and for the average change across all 3 collection bouts.)
- Change in Serum Phosphorus (PO4)(Serum PO4 is measured before and 15 minutes after the end of the 60 minute exercise bout at the 1st, 8th, and 16th exercise bout. Overall change across all 3 visits is also reported.)
- Change in Hematocrit (Hct)(Hct is measured before and 15 minutes after the 60 minutes of exercise to correct for plasma volume shifts at the 1st, 8th, and 16th exercise bout. Average change across all 3 exercise bouts is also provided.)
- Change in Hemoglobin (Hgb)(Hgb is measured before and 15 minutes after 60 minutes of exercise to correct for plasma volume shifts. Results are presented for the 1st, 8th, and 16th exercise bouts individually and the average across all 3 exercise collection bouts.)