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1.
Endocrinology ; 152(5): 1767-78, 2011 May.
Article in English | MEDLINE | ID: mdl-21343258

ABSTRACT

We compared teriparatide (TPTD) and strontium ranelate (SR) efficacy on bone formation activity in a mature rat model of estrogen-deficiency bone loss. Rats were ovariectomized (OVX) at age 6 months and permitted to lose bone for 2 months to establish osteopenia before initiation of treatment with TPTD (5 or 15 µg/kg · d sc) or SR (150 or 450 mg/kg · d oral gavage). After 3 wk, RT-PCR analyses of bone formation genes in the distal femur metaphysis showed significant elevation of collagen 1α2, osteocalcin, bone sialoprotein, alkaline phosphatase, and Runx2 gene expression at both TPTD doses, relative to OVX controls. SR had no significant effect on expression of these genes. TPTD treatment for 12 wk dose dependently increased lumbar vertebral (LV) and femoral midshaft bone mineral content (BMC) and bone mineral density over pretreatment and age-matched OVX controls. SR 150 increased BMC, and SR 450 increased BMC and bone mineral density of femoral midshaft and LV over OVX controls. There were significant dose-dependent TPTD increases of LV and femoral neck strength, and TPTD 15 also increased midshaft strength compared with pretreatment and age-matched OVX controls. SR did not enhance bone strength relative to pretreatment or age-matched OVX controls. Histomorphometry of the proximal tibial metaphysis showed dose-dependent effects of TPTD on trabecular area, number, width, and osteoblast surface, bone mineralizing surface, and bone formation rate relative to pretreatment and age-matched OVX controls, whereas SR had no effect on these parameters. These findings confirmed the bone anabolic efficacy of teriparatide, but not SR in mature, osteopenic, OVX rats.


Subject(s)
Bone Diseases, Metabolic/prevention & control , Bone and Bones/drug effects , Ovariectomy , Teriparatide/pharmacology , Alkaline Phosphatase/genetics , Anabolic Agents/pharmacology , Animals , Bone Density/drug effects , Bone Density Conservation Agents/pharmacology , Bone Diseases, Metabolic/blood , Bone Diseases, Metabolic/pathology , Bone and Bones/metabolism , Bone and Bones/pathology , Collagen Type I/genetics , Core Binding Factor Alpha 1 Subunit/genetics , Dose-Response Relationship, Drug , Female , Femur/drug effects , Femur/metabolism , Gene Expression/drug effects , Humans , Integrin-Binding Sialoprotein/genetics , Lumbar Vertebrae/drug effects , Lumbar Vertebrae/metabolism , Organometallic Compounds/pharmacology , Osteocalcin/blood , Osteocalcin/genetics , Rats , Reverse Transcriptase Polymerase Chain Reaction , Thiophenes/pharmacology , Time Factors
2.
Bone ; 46(4): 935-9, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20060081

ABSTRACT

The purpose of this post hoc analysis was to determine whether baseline concentrations or early changes in serum bone turnover markers were correlated with changes in bone mineral density (BMD) at 18 months in patients with glucocorticoid-induced osteoporosis (GIO) treated with teriparatide (n=80; 20 mug/day) or alendronate (n=77; 10 mg/day). Bone markers included type I collagen N-terminal propeptide (PINP), type I collagen C-terminal propeptide (PICP), bone alkaline phosphatase (bone ALP), and cross-linked C-telopeptide of type I collagen (Sbeta-CTX). The relationship between baseline and early changes in markers and the 18-month changes in lumbar spine (LS) and femoral neck (FN) BMD was evaluated using Spearman correlation analysis. In the teriparatide group, increases in LS and FN BMD at 18 months were not significantly correlated with baseline marker concentrations (P>0.05) but were correlated with the increases in PINP at 1 and 6 months (P<0.05). In the alendronate group, the increase in FN BMD at 18 months was positively correlated with baseline marker concentrations (P<0.05) and negatively correlated with change in PINP and Sbeta-CTX at 1 and 6 months. In addition, in the alendronate group, the increase in LS BMD was negatively correlated with change in Sbeta-CTX at 1 month (P<0.05). Increases in BMD at the spine and hip were independent of baseline bone turnover in the teriparatide group, while increases in hip BMD were dependent on baseline bone turnover in the alendronate group. With both therapies, early changes in some bone turnover markers were correlated with 18-month gains in BMD in patients with GIO.


Subject(s)
Alendronate/therapeutic use , Bone Density/drug effects , Bone Remodeling/drug effects , Glucocorticoids/adverse effects , Osteoporosis/drug therapy , Osteoporosis/metabolism , Teriparatide/therapeutic use , Alkaline Phosphatase/blood , Analysis of Variance , Biomarkers/blood , Bone Density/physiology , Bone Remodeling/physiology , Collagen Type I/blood , Double-Blind Method , Femur Neck/drug effects , Femur Neck/metabolism , Humans , Lumbar Vertebrae/drug effects , Lumbar Vertebrae/metabolism , Osteoporosis/chemically induced , Peptide Fragments/blood , Peptides/blood , Procollagen/blood
3.
J Bone Miner Res ; 25(2): 404-14, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19594305

ABSTRACT

Animal experiments show a dramatic improvement in skeletal repair by teriparatide. We tested the hypothesis that recombinant teriparatide, at the 20 microg dose normally used for osteoporosis treatment or higher, would accelerate fracture repair in humans. Postmenopausal women (45 to 85 years of age) who had sustained a dorsally angulated distal radial fracture in need of closed reduction but no surgery were randomly assigned to 8 weeks of once-daily injections of placebo (n = 34) or teriparatide 20 microg (n = 34) or teriparatide 40 microg (n = 34) within 10 days of fracture. Hypotheses were tested sequentially, beginning with the teriparatide 40 microg versus placebo comparison, using a gatekeeping strategy. The estimated median time from fracture to first radiographic evidence of complete cortical bridging in three of four cortices was 9.1, 7.4, and 8.8 weeks for placebo and teriparatide 20 microg and 40 microg, respectively (overall p = .015). There was no significant difference between the teriparatide 40 microg versus placebo groups (p = .523). In post hoc analyses, there was no significant difference between teriparatide 40 microg versus 20 microg (p = .053); however, the time to healing was shorter in teriparatide 20 microg than placebo (p = .006). The primary hypothesis that teriparatide 40 microg would shorten the time to cortical bridging was not supported. The shortened time to healing for teriparatide 20 microg compared with placebo still may suggest that fracture repair can be accelerated by teriparatide, but this result should be interpreted with caution and warrants further study.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Fractures, Bone/drug therapy , Teriparatide/therapeutic use , Aged , Aged, 80 and over , Bone Density/drug effects , Bone Density Conservation Agents/pharmacology , Double-Blind Method , Female , Fracture Healing/drug effects , Fractures, Bone/etiology , Humans , Injections, Subcutaneous , Middle Aged , Osteoporosis, Postmenopausal/complications , Osteoporosis, Postmenopausal/drug therapy , Radius Fractures/drug therapy , Radius Fractures/etiology , Teriparatide/pharmacology , Time Factors , Treatment Outcome
4.
Curr Med Res Opin ; 25(10): 2413-22, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19656016

ABSTRACT

OBJECTIVE: To determine functionality and acceptability of a new teriparatide (Forteo, Eli Lilly and Company, Indianapolis, IN, USA) delivery device by patients with osteoporosis. RESEARCH DESIGN AND METHODS: This was an eight week, single-arm, multicenter, open-label clinical trial. Patients received teriparatide 20 microg/day by subcutaneous injection using a new delivery device. Men and postmenopausal women with osteoporosis at high risk for fracture were stratified to Current User (n = 92) or Not Current User (n = 107) groups. Current Users had used the original delivery device for > or =8 weeks, including uninterrupted use for four weeks before enrollment. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT00577863. MAIN OUTCOME MEASURES: The primary objective was to detect common complaints (> or =3% for all patients) regarding the functionality and acceptability of the new device. Complaints were categorized as functional (e.g., malfunction), nonfunctional (e.g., size), or user manual. Secondary objectives included questionnaire assessment of preference of the new versus original device, features of the new delivery device, and analysis of adverse events. RESULTS: A total of 31 patients (16%) reported 47 complaints (four functional, 27 nonfunctional, and 16 user manual). There were two common complaints: device size (4.0%) and lack of information on alcohol swabs (3.5%). Overall, patients agreed that the new device was easy to use (99.5%), easy to learn to use (99%), easy to attach a needle (97%), easy to hold while injecting (95%), and that it reduced their reluctance to take injections (90%). Most Current Users (92%) preferred the new delivery device over the original device. Adverse events reported by > or =2% of patients were upper respiratory infection (3.5%), urinary tract infection (2%), influenza (2%), and headache (2%). Limitations include the one-arm study design and the short (eight week) duration of the study. CONCLUSIONS: Patients found the new teriparatide delivery device easy to use and Current Users preferred the new delivery device over the original device.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Drug Delivery Systems , Osteoporosis/drug therapy , Teriparatide/therapeutic use , Aged , Bone Density Conservation Agents/administration & dosage , Bone Density Conservation Agents/adverse effects , Female , Humans , Male , Prospective Studies , Teriparatide/administration & dosage , Teriparatide/adverse effects
5.
Curr Med Res Opin ; 24(11): 3117-28, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18838053

ABSTRACT

OBJECTIVE: Recombinant teriparatide, a bone anabolic agent, is given to treatment-naïve and pre-treated patients with severe osteoporosis, but few data exist comparing the response to teriparatide in these groups. EUROFORS (the EUROpean study of FORSteo‡) enrolled postmenopausal women with established osteoporosis who were either treatment-naïve or had prior antiresorptive (AR) treatment with or without documented inadequate clinical response. The objective of the secondary analysis described here was to evaluate the interim bone mineral density (BMD) response in these groups after one year of open-label teriparatide therapy. RESEARCH DESIGN AND METHODS: Postmenopausal women with established osteoporosis who enrolled in a prospective, randomized, controlled trial received open-label teriparatide 20 µg/day for the first year. With respect to their prior osteoporosis treatment history, they were retrospectively allocated to one of three groups: treatment-naïve (n = 204), prior treatment with an antiresorptive drug (AR-pretreated) (n = 240), or prior antiresorptive treatment with inadequate response (inadequate AR-responders) (n = 421). BMD was measured by dual energy x-ray absorptiometry. RESULTS: Lumbar spine BMD increased from baseline (p < 0.001) in the three groups (mean, 95% CI); treatment-naïve: 8.4% (7.4%, 9.3%); AR-pretreated: 7.1% (6.3%, 7.9%); inadequate AR-responders: 6.2% (5.6%, 6.9%). Total hip BMD increased from baseline in the treatment-naïve (p < 0.001): 1.8% (1.1%, 2.5%) but did not change in the AR-pretreated: 0.4% (-0.2%, 1.1%) or inadequate AR-responders: -0.3% (-0.9%, 0.2%). Treatment-emergent adverse events were similar in the three groups. CONCLUSION: One year of teriparatide significantly (p < 0.001) increased spine BMD in all groups, and total hip BMD in the treatment-naïve group. Because of the limitations of this interim analysis (most importantly, the short duration of treatment and lack of a control group), further study is needed to determine the optimal treatment duration to reach the potential BMD gains at the proximal femur in patients with prior antiresorptive drug use (mostly bisphosphonates). CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, nct00191425.


Subject(s)
Bone Density/drug effects , Osteoporosis, Postmenopausal/drug therapy , Teriparatide/therapeutic use , Aged , Algorithms , Bone Density/physiology , Bone Density Conservation Agents/therapeutic use , Chemotherapy, Adjuvant , Europe , Female , Femur Neck/drug effects , Hip , Humans , Lumbar Vertebrae/drug effects , Middle Aged , Neoadjuvant Therapy , Osteoporosis, Postmenopausal/physiopathology , Treatment Outcome
6.
N Engl J Med ; 357(20): 2028-39, 2007 Nov 15.
Article in English | MEDLINE | ID: mdl-18003959

ABSTRACT

BACKGROUND: Bisphosphonate therapy is the current standard of care for the prevention and treatment of glucocorticoid-induced osteoporosis. Studies of anabolic therapy in patients who are receiving long-term glucocorticoids and are at high risk for fracture are lacking. METHODS: In an 18-month randomized, double-blind, controlled trial, we compared teriparatide with alendronate in 428 women and men with osteoporosis (ages, 22 to 89 years) who had received glucocorticoids for at least 3 months (prednisone equivalent, 5 mg daily or more). A total of 214 patients received 20 microg of teriparatide once daily, and 214 received 10 mg of alendronate once daily. The primary outcome was the change in bone mineral density at the lumbar spine. Secondary outcomes included changes in bone mineral density at the total hip and in markers of bone turnover, the time to changes in bone mineral density, the incidence of fractures, and safety. RESULTS: At the last measurement, the mean (+/-SE) bone mineral density at the lumbar spine had increased more in the teriparatide group than in the alendronate group (7.2+/-0.7% vs. 3.4+/-0.7%, P<0.001). A significant difference between the groups was reached by 6 months (P<0.001). At 12 months, bone mineral density at the total hip had increased more in the teriparatide group. Fewer new vertebral fractures occurred in the teriparatide group than in the alendronate group (0.6% vs. 6.1%, P=0.004); the incidence of nonvertebral fractures was similar in the two groups (5.6% vs. 3.7%, P=0.36). Significantly more patients in the teriparatide group had at least one elevated measure of serum calcium. CONCLUSIONS: Among patients with osteoporosis who were at high risk for fracture, bone mineral density increased more in patients receiving teriparatide than in those receiving alendronate. (ClinicalTrials.gov number, NCT00051558 [ClinicalTrials.gov].).


Subject(s)
Alendronate/therapeutic use , Bone Density Conservation Agents/therapeutic use , Bone Density/drug effects , Glucocorticoids/adverse effects , Osteoporosis/drug therapy , Teriparatide/therapeutic use , Aged , Aged, 80 and over , Alendronate/adverse effects , Alendronate/pharmacology , Biomarkers/blood , Bone Density Conservation Agents/adverse effects , Bone Density Conservation Agents/pharmacology , Bone Remodeling/drug effects , Calcium/blood , Double-Blind Method , Female , Fractures, Bone/epidemiology , Fractures, Bone/prevention & control , Humans , Lumbar Vertebrae/drug effects , Lumbar Vertebrae/physiology , Male , Middle Aged , Osteoporosis/chemically induced , Risk , Teriparatide/adverse effects , Teriparatide/pharmacology
7.
J Bone Miner Res ; 21(6): 855-64, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16753016

ABSTRACT

UNLABELLED: Transiliac bone biopsies were obtained from 55 women treated with teriparatide or placebo for 12-24 months. We report direct evidence that modeling bone formation at quiescent surfaces was present only in teriparatide-treated patients and bone formation at remodeling sites was higher with teriparatide than placebo. INTRODUCTION: Recombinant teriparatide [human PTH(1-34)], a bone formation agent for the treatment of osteoporosis when given once daily subcutaneously, increases biochemical markers of bone turnover and activation frequency in histomorphometry studies. MATERIALS AND METHODS: We studied the mechanisms underlying this bone-forming action of teriparatide at the basic multicellular unit by the appearance of cement lines, a method used to directly classify surfaces as modeling or remodeling osteons, and by the immunolocalization of IGF-I and IGF-II. Transiliac bone biopsies were obtained from 55 postmenopausal women treated with teriparatide 20 or 40 microg or placebo for 12-24 months (median, 19.8 months) in the Fracture Prevention Trial. RESULTS: A dose-dependent relationship was observed in modeling and mixed remodeling/modeling trabecular hemiosteons. Trabecular and endosteal hemiosteon mean wall thicknesses were significantly higher in both teriparatide groups than in placebo. There was a dose-dependent relationship in IGF-II immunoreactive staining at all bone envelopes studied. The greater local IGF-II presence after treatment with teriparatide may play a key role in stimulating bone formation. CONCLUSIONS: Direct evidence is presented that 12-24 months of teriparatide treatment induced modeling bone formation at quiescent surfaces and resulted in greater bone formation at remodeling sites, relative to placebo.


Subject(s)
Bone Remodeling/drug effects , Haversian System/ultrastructure , Insulin-Like Growth Factor II/metabolism , Osteogenesis/drug effects , Osteoporosis, Postmenopausal/drug therapy , Teriparatide/therapeutic use , Aged , Bone Density Conservation Agents/therapeutic use , Bone Remodeling/physiology , Bone and Bones/chemistry , Bone and Bones/drug effects , Demography , Dose-Response Relationship, Drug , Female , Haversian System/growth & development , Humans , Immunohistochemistry , Insulin-Like Growth Factor II/chemistry , Postmenopause
8.
J Bone Miner Res ; 20(9): 1507-13, 2005 Sep.
Article in English | MEDLINE | ID: mdl-16059622

ABSTRACT

UNLABELLED: A follow-up in 1262 women was conducted after the discontinuation of teriparatide. The hazard ratio for combined teriparatide group (20 and 40 microg) for the 50-month period after baseline was 0.57 (p = 0.002), suggesting a sustained effect in reducing the risk of nonvertebral fragility fracture. INTRODUCTION: Treatment with teriparatide [rhPTH(1-34)] 20 and 40 microg once-daily subcutaneous dosing significantly reduced the risk of nonvertebral fragility fractures over a median exposure of 19 months. MATERIALS AND METHODS: All participants in the Fracture Prevention Trial were invited to participate in a follow-up study. Prior treatment assignments were revealed, and patients were able to receive osteoporosis treatments without restriction. RESULTS: Approximately 60% of the 1262 patients received an osteoporosis treatment at some time during follow-up, with greater use in the former placebo group than in the combined former teriparatide group (p < 0.05). The hazard ratios for nonvertebral fragility fractures in each teriparatide group relative to placebo were statistically significant for the 50-month period including treatment and follow-up (p < 0.03). In the follow-up period, the hazard ratio was significantly different between the 40 mug and combined groups versus placebo but not for the 20 microg group versus placebo. However, the 20 and 40 microg groups were not different from each other. Kaplan-Meier analysis of time to fracture showed that the fracture incidence in the former placebo and teriparatide groups diverged during the 50-month period including teriparatide treatment and follow-up (p = 0.009). Total hip and femoral neck BMD decreased in teriparatide-treated patients who had no follow-up treatment; BMD remained stable or further increased in patients who received a bisphosphonate after teriparatide treatment. CONCLUSIONS: While the study design is observational, the results support a sustained effect of teriparatide in reducing the risk of nonvertebral fragility fractures up to 30 months after discontinuation of treatment.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Fractures, Bone/prevention & control , Osteoporosis, Postmenopausal/drug therapy , Teriparatide/therapeutic use , Aged , Analysis of Variance , Bone Density , Bone Density Conservation Agents/administration & dosage , Diphosphonates/metabolism , Double-Blind Method , Female , Follow-Up Studies , Fracture Healing , Hip/pathology , Humans , Middle Aged , Osteoporosis , Placebos , Proportional Hazards Models , Risk , Teriparatide/administration & dosage , Time Factors
9.
Arch Intern Med ; 165(15): 1762-8, 2005.
Article in English | MEDLINE | ID: mdl-16087825

ABSTRACT

BACKGROUND: Antiresorptive agents for the treatment of osteoporosis suppress bone remodeling and reestablish bone turnover at a lower rate to reduce bone loss. Recombinant teriparatide (human parathyroid hormone 1-34) stimulates bone formation, increases bone mass, and improves bone microarchitecture. We contrasted the effects of once-daily doses of 20 mug of teriparatide and 10 mg of alendronate sodium on bone mineral density (BMD) and markers of bone turnover. METHODS: Markers of bone turnover and areal BMD were assessed in 203 postmenopausal women with osteoporosis in an 18-month randomized parallel double-blind study; volumetric BMD was measured in a subset of women. RESULTS: Teriparatide significantly increased markers of bone turnover that peaked at 6 months (serum procollagen type I N-terminal propeptide, 218%, and urinary N-telopeptide corrected for creatinine, 58%; P<.001); alendronate significantly decreased the markers at 6 months (-67% and -72%, respectively; P<.001). At 18 months, areal and volumetric spine BMDs were significantly higher with teriparatide than with alendronate (10.3% vs 5.5% [P<.001] and 19.0% vs 3.8% [P<.01], respectively). Areal femoral neck BMD was significantly higher than baseline in the teriparatide and alendronate groups (3.9% and 3.5%, respectively). There were no significant differences in trabecular femoral neck BMD between the teriparatide and alendronate groups (4.9% and 2.2%, respectively). Cortical volumetric femoral neck BMD was significantly different between the teriparatide and alendronate groups (-1.2% and 7.7%, respectively; P = .05). CONCLUSION: Two distinct options for the management of osteoporosis lead to increases in BMD by opposite mechanisms of action on bone remodeling.


Subject(s)
Alendronate/pharmacology , Bone Remodeling/drug effects , Teriparatide/pharmacology , Aged , Aged, 80 and over , Bone Density/drug effects , Collagen/urine , Collagen Type I , Female , Humans , Middle Aged , Peptide Fragments/blood , Peptides/urine , Procollagen/blood
10.
J Bone Miner Res ; 20(7): 1244-53, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15940379

ABSTRACT

UNLABELLED: An 18-month randomized double-blind study was conducted in postmenopausal women with osteoporosis to compare the effects of once-daily teriparatide 20 microg with alendronate 10 mg on bone histomorphometry. Biopsies were obtained from 42 patients. Indices of bone formation were significantly higher after 6 or 18 months of teriparatide compared with alendronate treatment. INTRODUCTION: Alendronate and teriparatide increased BMD, assessed by DXA, by different mechanisms of action, supported by changes in biochemical markers of bone turnover. The purpose of this cross-sectional study was to explore the differential effects of these two osteoporosis treatments at the bone tissue level by examining bone histomorphometric parameters of bone turnover after either 6 or 18 months of treatment. MATERIALS AND METHODS: Patients were a cohort from a randomized parallel double-blind study conducted to compare the effects of once-daily teriparatide 20 microg and alendronate 10 mg in postmenopausal women with osteoporosis. Transiliac crest bone biopsies were obtained after tetracycline double labeling from 42 patients treated for 6 months (n = 23) or 18 months (n = 14); 5 additional patients were biopsied from contralateral sides at 6 and 18 months. Biopsy specimens adequate for quantitative analysis were analyzed by 2D histomorphometry from 17 patients at 6 months (teriparatide, n = 8; alendronate, n = 9) and 15 patients at 18 months (teriparatide, n = 8; alendronate, n = 7). Data were analyzed by two-sample tests. RESULTS: Histomorphometric indices of bone formation were significantly and markedly greater in the teriparatide group than in the alendronate group at 6 and 18 months, whereas indices of bone resorption were only significantly greater in the teriparatide group than in the alendronate group at 6 months. Bone formation and activation frequency were significantly lower at 18 months compared with 6 months in the teriparatide group, returning to levels comparable with untreated postmenopausal women. In the teriparatide group, the peak in histomorphometric bone formation indices coincided with peak levels for N-terminal propeptide of type I collagen, a biochemical marker of bone formation. The degree of mineralization was lower at 18 months than at 6 months with treatment in both groups but was not different between groups. CONCLUSIONS: These results confirm the opposite mechanisms of action of teriparatide and alendronate on bone remodeling and confirm the bone formation effect of teriparatide.


Subject(s)
Alendronate/therapeutic use , Bone Remodeling/drug effects , Osteoporosis, Postmenopausal/drug therapy , Teriparatide/therapeutic use , Absorptiometry, Photon , Aged , Biomarkers/analysis , Bone Density/drug effects , Calcification, Physiologic/drug effects , Female , Humans , Ilium/pathology , Middle Aged , Postmenopause/drug effects , Postmenopause/metabolism
11.
Phys Sportsmed ; 10(2): 93-97, 1982 Feb.
Article in English | MEDLINE | ID: mdl-29261086

ABSTRACT

In brief The six collegiate male volleyball players in this study had moderate aerobic capacity (56 ml·kg-1·min-1) and predominantly fast twitch fiber distribution (57%) in the vastus lateralis muscle. Prolonged volleyball play resulted in a greater depletion of glycogen in slow twitch fibers than in fast twitch and no hint of anaerobic fatigue. These results suggest that in spite of the apparent explosive activity of volleyball, the overall intensity is probably mild to moderate and therefore aerobic endurance may be critical to performance.

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