-
1.
Anabolic Bone Stimulus Requires a Pre-Exercise Meal and 45-Minute Walking Impulse of Suprathreshold Speed-Enhanced Momentum to Prevent or Mitigate Postmenopausal Osteoporosis within Circadian Constraints.
Zheng, Q, Kernozek, T, Daoud-Gray, A, Borer, KT
Nutrients. 2021;(11)
Abstract
Osteoporosis currently afflicts 8 million postmenopausal women in the US, increasing the risk of bone fractures and morbidity, and reducing overall quality of life. We sought to define moderate exercise protocols that can prevent postmenopausal osteoporosis. Our previous findings singled out higher walking speed and pre-exercise meals as necessary for suppression of bone resorption and increasing of markers of bone formation. Since both studies were amenable to alternate biomechanical, nutritional, and circadian interpretations, we sought to determine the relative importance of higher speed, momentum, speed-enhanced load, duration of impulse, and meal timing on osteogenic response. We hypothesized that: (1) 20 min of exercise one hour after eating is sufficient to suppress bone resorption as much as a 40-min impulse and that two 20 min exercise bouts separated by 7 h would double the anabolic effect; (2) early morning exercise performed after eating will be as effective as mid-day exercise for anabolic outcome; and (3) the 08:00 h 40-min. exercise uphill would be as osteogenic as the 40-min exercise downhill. Healthy postmenopausal women, 8 each, were assigned to a no-exercise condition (SED) or to 40- or 20-min exercise bouts, spaced 7 h apart, for walking uphill (40 Up and 20 Up) or downhill (40 Down and 20 Down) to produce differences in biomechanical variables. Exercise was initiated at 08:00 h one hour after eating in 40-min groups, and also 7 h later, two hours after the midday meal, in 20-min groups. Measurements were made of CICP (c-terminal peptide of type I collagen), osteocalcin (OC), and bone-specific alkaline phosphatase (BALP), markers of bone formation, and of the bone resorptive marker CTX (c-terminal telopeptide of type 1 collagen). The osteogenic ratios CICP/CTX, OC/CTX, and BALP/CTX were calculated. Only the 40-min downhill exercise of suprathreshold speed-enhanced momentum, increased the three osteogenic ratios, demonstrating the necessity of a 40-min, and inadequacy of a 20-min, exercise impulse. The failure of anabolic outcome in 40-min uphill exercise was attributed to a sustained elevation of PTH concentration, as its high morning elevation enhances the CTX circadian rhythm. We conclude that postmenopausal osteoporosis can be prevented or mitigated in sedentary women by 45 min of morning exercise of suprathreshold speed-enhanced increased momentum performed shortly after a meal while walking on level ground, or by 40-min downhill, but not 40-min uphill, exercise to avoid circadian PTH oversecretion. The principal stimulus for the anabolic effect is exercise, but the prerequisite for a pre-exercise meal demonstrates the requirement for nutrient facilitation.
-
2.
Nutritional Therapy with Vitamin K1 Is Effective in the Improvement of Vitamin K Status and Bone Turnover Markers in Patients with Severe Motor and Intellectual Disabilities.
Kuwabara, A, Nagae, A, Kitagawa, M, Tozawa, K, Kumode, M, Tanaka, K
Journal of nutritional science and vitaminology. 2020;(3):278-284
Abstract
We have previously reported that patients with severe motor and intellectual disabilities (SMID) have a high prevalence of vitamin K deficiency both in the liver and bone. Thus, vitamin K therapy for SMID patients should be considered. In the present study, we have studied the efficacy of nutritional therapy with vitamin K1 for improving their vitamin K status and bone metabolism markers in patients with SMID. During the 3-mo period, 19 patients under enteral feeding received vitamin K1 treatment, the dose of which was determined to meet each subject's energy requirement. Biomarkers of vitamin K insufficiency; protein induced by vitamin K absence or antagonist-II (PIVKA-II), undercarboxylated osteocalcin (ucOC), intact osteocalcin (intact OC) and bone turnover markers (tartrate-resistant acid phosphatase-5b: TRACP-5b and bone alkaline phosphatase: BAP) were measured at baseline and post treatment. The ucOC/OC ratio was calculated as a more sensitive index than ucOC for vitamin K status in the bone. After treatment, the median vitamin K intake increased from 66 to 183 μg/d, and serum levels of PIVKA-II and ucOC/OC ratio were significantly decreased. Decrements of serum ucOC level and ucOC/OC ratio were significantly associated with vitamin K intake, indicating that both markers well reflect the dose-dependent vitamin K effects. Serum levels of BAP and TRACP-5b were significantly increased after vitamin K1 therapy. Nutritional therapy with vitamin K1 effectively improved the markers for vitamin K status and bone turnover, and was considered to be a good candidate for treatment in SMID patients.
-
3.
Efficacy and Safety of Asfotase Alfa in Infants and Young Children With Hypophosphatasia: A Phase 2 Open-Label Study.
Hofmann, CE, Harmatz, P, Vockley, J, Högler, W, Nakayama, H, Bishop, N, Martos-Moreno, GÁ, Moseley, S, Fujita, KP, Liese, J, et al
The Journal of clinical endocrinology and metabolism. 2019;(7):2735-2747
-
-
Free full text
-
Abstract
CONTEXT Long-term data on enzyme replacement treatment of hypophosphatasia (HPP) are limited. OBJECTIVE To evaluate efficacy and safety of asfotase alfa in patients aged ≤5 years with HPP followed for up to 6 years. DESIGN Phase 2 open-label study (July 2010 to September 2016). SETTING Twenty-two sites; 12 countries. PARTICIPANTS Sixty-nine patients [median (range) age: 16.0 (0.02 to 72) months] with severe HPP and sign/symptom onset before age 6 months. INTERVENTION Asfotase alfa 2 mg/kg three times/week or 1 mg/kg six times/week subcutaneously. MAIN OUTCOME MEASURES Primary efficacy measure: Radiographic Global Impression of Change (RGI-C) score [-3 (severe worsening) to +3 (complete/near-complete healing)]. Additional outcome measures: respiratory status, growth, and safety. Post hoc analysis: characteristics of radiographic responders vs nonresponders at Year 1 (RGI-C: ≥+2 vs <+2). RESULTS During median (minimum, maximum) 2.3 (0.02, 5.8) years of treatment, RGI-C scores improved significantly at Month 6 [+2.0 (-1.7, +3.0)], Year 1 [+2.0 (-2.3, +3.0)], and Last Assessment [+2.3 (-2.7, +3.0); P < 0.0001 all]. Of 24 patients requiring respiratory support at Baseline, 11 (46%) no longer needed support. Height/weight z scores generally increased. Nine patients died (13%). All patients experienced at least one adverse event; pyrexia was most common. Compared with responders [n = 50 (72%)], nonresponders [n = 19 (28%)] had more severe disease at Baseline and a higher rate of neutralizing antibodies (NAbs) at Last Assessment. CONCLUSIONS Most infants/young children given asfotase alfa showed early radiographic and clinical improvement sustained up to 6 years; radiographic nonresponders had more severe disease and more frequent NAbs at Last Assessment.
-
4.
No Added Value of 18F-Sodium Fluoride PET/CT for the Detection of Bone Metastases in Patients with Newly Diagnosed Prostate Cancer with Normal Bone Scintigraphy.
Zacho, HD, Jochumsen, MR, Langkilde, NC, Mortensen, JC, Haarmark, C, Hendel, HW, Jensen, JB, Petersen, LJ
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2019;(12):1713-1716
Abstract
The aim of this study was to determine if additional 18F-sodium fluoride PET/CT (NaF PET/CT) improves the prognostic accuracy in the initial staging of prostate cancer patients with normal bone scintigraphy undergoing prostatectomy. Methods: A prospective cohort study examined NaF PET/CT in intermediate- or high-risk prostate cancer with negative bone scintigraphy who were scheduled for prostatectomy. Biochemical response: PSA levels < 0.2 ng/mL at 6 wk and 6 mo postoperatively, PSA level ≥ 0.2 ng/mL was biochemical failure. Results: Eighty-one patients were included in the study; 75 patients (93%) achieved biochemical responses, 6 patients had biochemical failure. NaF PET/CT indicated bone metastasis in 1 patient (1.2%), was equivocal in 7 patients (8.6%), without bone metastases in 73 patients (90.1%). Eight patients with bone metastases or equivocal results on NaF PET/CT exhibited biochemical responses. All patients with biochemical failure had negative NaF PET/CT and bone scintigraphy for bone metastases. Conclusion: NaF PET/CT has no added value for bone staging in intermediate- and high-risk prostate cancer patients with normal bone scintigraphy results undergoing prostatectomy.
-
5.
Treatment of thoracic or lumbar burst fractures with Balloon Assisted Endplate Reduction using Tricalcium Phosphate cement: histological and radiological evaluation.
Kitzen, J, Schotanus, MGM, Plasschaert, HSW, Hulsmans, FH, Tilman, PBJ
BMC musculoskeletal disorders. 2017;(1):411
Abstract
BACKGROUND Short-segment pedicle-screw instrumentation is frequently used to stabilize thoracolumbar burst fractures. A recognized disadvantage of this procedure is recurrent kyphosis from intervertebral disc creep into the fractured central endplate. Balloon Assisted Endplate Reduction (BAER) using Tricalcium Phosphate bone cement (TCP) enables elevation of the centrally depressed endplate. Our objective was to evaluate the bone-tissue response to TCP and to analyse whether BAER using TCP can prevent recurrent kyphosis after removal of the instrumentation. METHODS Fourteen patients with traumatic thoracolumbar burst fractures were operated with BAER using TCP in combination with short-segment instrumentation. Nine months after surgery, instrumentation was removed and transpedicular biopsies were taken for histological and histochemical analysis. Roentgenograms pre- and postoperatively and at latest follow-up after removal of the instrumentation were evaluated. RESULTS Average follow-up was 2.6 years. Analysis of the biopsies showed a variable degree of bone remodelling with incorporation of TCP into newly formed bone matrix. No extensive foreign body reactions, inflammation, granulomatous responses or tissue necrosis were observed. Wedge-angle, kyphosis-angle and both the anterior-posterior and central-posterior vertebral body height ratios improved significant postoperatively (p < 0.001). After removal of the instrumentation no significant differences in wedge-angle or height ratios were seen (p = 0.12). The kyphosis-angle increased four degrees (p = 0.01). CONCLUSION TCP showed good histological osseointegration with no adverse events. TCP can therefore be safely used and could be beneficial in treatment of thoracolumbar burst fractures. BAER with TCP in combination with short-segment instrumentation might reduce recurrence of deformity even after removal of the instrumentation in comparison to short-segment instrumentation alone. TRIAL REGISTRATION This study is registered at the at the Dutch Trial Registry (NTR3498).
-
6.
On the combined effects of normobaric hypoxia and bed rest upon bone and mineral metabolism: Results from the PlanHab study.
Rittweger, J, Debevec, T, Frings-Meuthen, P, Lau, P, Mittag, U, Ganse, B, Ferstl, PG, Simpson, EJ, Macdonald, IA, Eiken, O, et al
Bone. 2016;:130-8
Abstract
Bone losses are common as a consequence of unloading and also in patients with chronic obstructive pulmonary disease (COPD). Although hypoxia has been implicated as an important factor to drive bone loss, its interaction with unloading remains unresolved. The objective therefore was to assess whether human bone loss caused by unloading could be aggravated by chronic hypoxia. In a cross-over designed study, 14 healthy young men underwent 21-day interventions of bed rest in normoxia (NBR), bed rest in hypoxia (HBR), and hypoxic ambulatory confinement (HAmb). Hypoxic conditions were equivalent to 4000m altitude. Bone metabolism (NTX, P1NP, sclerostin, DKK1) and phospho-calcic homeostasis (calcium and phosphate serum levels and urinary excretion, PTH) were assessed from regular blood samples and 24-hour urine collections, and tibia and femur bone mineral content was assessed by peripheral quantitative computed tomography (pQCT). Urinary NTX excretion increased (P<0.001) to a similar extent in NBR and HBR (P=0.69) and P1NP serum levels decreased (P=0.0035) with likewise no difference between NBR and HBR (P=0.88). Serum total calcium was increased during bed rest by 0.059 (day D05, SE 0.05mM) to 0.091mM (day D21, P<0.001), with no additional effect by hypoxia during bed rest (P=0.199). HAmb led, at least temporally, to increased total serum calcium, to reduced serum phosphate, and to reduced phosphate and calcium excretion. In conclusion, hypoxia did not aggravate bed rest-induced bone resorption, but led to changes in phospho-calcic homeostasis likely caused by hyperventilation. Whether hyperventilation could have mitigated the effects of hypoxia in this study remains to be established.
-
7.
Short-Term Effects of Kefir-Fermented Milk Consumption on Bone Mineral Density and Bone Metabolism in a Randomized Clinical Trial of Osteoporotic Patients.
Tu, MY, Chen, HL, Tung, YT, Kao, CC, Hu, FC, Chen, CM
PloS one. 2015;(12):e0144231
Abstract
UNLABELLED Milk products are good sources of calcium that may reduce bone resorption and help prevent bone loss as well as promote bone remodeling and increase bone formation. Kefir is a product made by kefir grains that degrade milk proteins into various peptides with health-promoting effects, including antithrombotic, antimicrobial and calcium-absorption enhancing bioactivities. In a controlled, parallel, double-blind intervention study over 6 months, we investigated the effects of kefir-fermented milk (1,600 mg) supplemented with calcium bicarbonate (CaCO3, 1,500 mg) and bone metabolism in 40 osteoporosis patients, and compared them with CaCO3 alone without kefir supplements. Bone turnover markers were measured in fasting blood samples collected before therapy and at 1, 3, and 6 months. Bone mineral density (BMD) values at the spine, total hip, and hip femoral neck were assessed by dual-energy x-ray absorptiometry (DXA) at baseline and at 6 months. Among patients treated with kefir-fermented milk, the relationships between baseline turnover and 6 months changes in DXA-determined BMD were significantly improved. The serum β C-terminal telopeptide of type I collagen (β-CTX) in those with T-scores > -1 patients significantly decreased after three months treatment. The formation marker serum osteocalcin (OC) turned from negative to positive after 6 months, representing the effect of kefir treatment. Serum parathyroid hormone (PTH) increased significantly after treatment with kefir, but decreased significantly in the control group. PTH may promote bone remodeling after treatment with kefir for 6 months. In this pilot study, we concluded that kefir-fermented milk therapy was associated with short-term changes in turnover and greater 6-month increases in hip BMD among osteoporotic patients. TRIAL REGISTRATION ClinicalTrials.gov NCT02361372.
-
8.
The effect of a prevention program based on health belief model on osteoporosis.
Khani Jeihooni, A, Hidarnia, A, Kaveh, MH, Hajizadeh, E
Journal of research in health sciences. 2015;(1):47-53
Abstract
BACKGROUND Osteoporosis is one of the most common metabolic bone diseases. The purpose of this study was to investigate the effect of a prevention program based on health belief model on osteoporosis among women. METHODS In this quasi-case study, 120 patients (60 cases and 60 control), registered under the health centers in Fasa City, Fars Province, Iran were selected in 2014. A questionnaire consisting of demographic information, Health Belief Model (HBM) constructs was used to measure nutrition and walking performance for prevention of osteoporosis before, immediately after the intervention and six months later. Bone mineral density (BMD) was recorded at the lumbar spine and femur before and six months after intervention. Data were analyzed using SPSS19 via chi-square test, independent t-test, and Repeated Measures ANOVA at significance level of 0.05. RESULTS Immediately and six months after the intervention, the case group showed a significant increase in the knowledge, perceived susceptibility, perceived severity, perceived benefits, perceived barriers, self-efficacy, internal cues to action, nutrition and walking performance compared to the control group. Six months after the intervention, the value of lumbar spine BMD T-Score in the case group increased to 0.127, while in the control group it reduced to -0.043. The value of the Hip BMD T-Score in the intervention group increased to 0.125 but it decreased to -0.028 in the control group. CONCLUSIONS This study showed the effectiveness of knowledge, walking and diet on bone mass by HBM model. Hence, these models can act as a framework for designing and implementing educational interventions for the osteoporosis prevention.
-
9.
Biomarker-calibrated protein intake and bone health in the Women's Health Initiative clinical trials and observational study.
Beasley, JM, LaCroix, AZ, Larson, JC, Huang, Y, Neuhouser, ML, Tinker, LF, Jackson, R, Snetselaar, L, Johnson, KC, Eaton, CB, et al
The American journal of clinical nutrition. 2014;(4):934-40
-
-
Free full text
-
Abstract
BACKGROUND The effects of dietary protein on bone health are controversial. OBJECTIVE We examined the relation between protein intake with fracture and bone mineral density (BMD) within the Women's Health Initiative (WHI). DESIGN This prospective analysis included 144,580 women aged 50-79 y at baseline in the WHI clinical trials (CTs) and observational study (OS) that recruited participants in 1993-1998 with follow-up through 2011. Self-reported clinical fractures were collected semiannually through the original end of the trials (WHI CTs) and annually (WHI OS) by questionnaires. Hip fracture was adjudicated by a central review of radiology reports. BMDs for total body, hip, and spine were measured at baseline and 3 and 6 y in 9062 women at 3 WHI clinics by using dual-energy X-ray absorptiometry. Protein intake was assessed via food-frequency questionnaire and calibrated by using biomarkers of energy and protein intakes. Associations between protein intake and fracture were estimated by using Cox proportional hazards regression, and the relation between protein intake and BMD was estimated by using linear regression. RESULTS Median biomarker-calibrated protein intake was 15% of energy intake. Per 20% increase in calibrated protein intake (percentage of energy), there was no significant association with total fracture (HR: 0.99; 95% CI: 0.97, 1.02) or hip fracture (HR: 0.91; 95% CI: 0.84, 1.00), but there was an inverse association with forearm fracture (HR: 0.93; 95% CI: 0.88, 0.98). Each 20% increase in calibrated protein intake was associated with a significantly higher BMD for total body (mean 3-y change: 0.003 g/cm²; 95% CI: 0.001, 0.005 g/cm²) and hip (mean 3-y change: 0.002 g/cm²; 95% CI: 0.001, 0.004 g/cm²). CONCLUSIONS Higher biomarker-calibrated protein intake within the range of usual intake was inversely associated with forearm fracture and was associated with better maintenance of total and hip BMDs. These data suggest higher protein intake is not detrimental to bone health in postmenopausal women.
-
10.
Effects of paricalcitol on calcium and phosphate metabolism and markers of bone health in patients with diabetic nephropathy: results of the VITAL study.
Coyne, DW, Andress, DL, Amdahl, MJ, Ritz, E, de Zeeuw, D
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2013;(9):2260-8
-
-
Free full text
-
Abstract
BACKGROUND Chronic kidney disease (CKD) is associated with elevations in serum phosphate, calcium-phosphorus product and bone-specific alkaline phosphatase (BAP), with attendant risks of cardiovascular and bone disorders. Active vitamin D can suppress parathyroid hormone (PTH), but may raise serum calcium and phosphate concentrations. Paricalcitol, a selective vitamin D activator, suppressed PTH in CKD patients (stages 3 and 4) with secondary hyperparathyroidism (SHPT) with minimal changes in calcium and phosphate metabolism. METHODS The VITAL study enrolled patients with CKD stages 2-4. We examined the effect and relationship of paricalcitol to calcium and phosphate metabolism and bone markers in a post hoc analysis of VITAL. The study comprised patients with diabetic nephropathy enrolled in a double-blind, placebo-controlled, randomized trial of paricalcitol (1 or 2 μg/day). Urinary and serum calcium and phosphate, serum BAP, and intact PTH (iPTH) concentrations were measured throughout the study. RESULTS Baseline demographics and calcium, phosphate, PTH (49% with iPTH <70 pg/mL), and BAP concentrations were similar between groups. A transient, modest yet significant increase in phosphate was observed for paricalcitol 2 μg/day (+0.29 mg/dL; P < 0.001). Dose-dependent increases in serum and urinary calcium were observed; however, there were few cases of hypercalcemia: one in the 1-μg/day group (1.1%) and three in the 2-μg/day group (3.2%). Significant reductions in BAP were observed that persisted for 60 days after paricalcitol discontinuation (P < 0.001 for combined paricalcitol groups versus placebo). Paricalcitol dose-dependent reductions in iPTH were observed. Paricalcitol in CKD patients (±SHPT) was associated with modest increases in calcium and phosphate. CONCLUSION Paricalcitol reduces BAP levels, which may be beneficial for reducing vascular calcification. TRIAL REGISTRATION Trial is registered with ClinicalTrials.gov, number NCT00421733.