PTH and bone material strength in hypoparathyroidism as measured by impact microindentation.

PTH levels might be associated with bone material strength as measured by impact microindentation. Resistance to microfracture is decreased in hypoparathyroidism and appears to be associated with more severe disease and to improve with PTH replacement. INTRODUCTION: PTH is a key regulator of bone structure and remodeling. When PTH is absent in hypoparathyroidism (HypoPT), bone mass is increased and remodeling is decreased. In addition to bone structure and remodeling, bone material properties contribute to fracture resistance. Yet little is known about the relationship between PTH and bone material properties. Impact microindentation provides a clinical assessment of microfracture resistance, measured as the bone material strength index (BMSi). METHODS: Case-control cross-sectional study of PTH levels and in vivo BMSi measurement by impact microindentation at the anterior tibia in HypoPT patients (n = 17) and in controls matched for age, sex, and menopausal status (n = 17), with follow-up in a subgroup of HypoPT patients (n = 5) after recombinant human parathyroid hormone (1-84) [rhPTH(1-84)] treatment. RESULTS: BMSi was positively associated with PTH levels in controls (r = 0.58, p = 0.02) and was 11% lower (p = 0.01) in HypoPT patients as compared with controls. In HypoPT, lower BMSi was associated with a trend toward greater supplemental calcium doses (p = 0.07). BMSi increased after rhPTH(1-84) treatment in the HypoPT patients who underwent repeat microindentation. CONCLUSIONS: PTH levels might be associated with bone material strength, although other factors might be contributory. In HypoPT, resistance to microfracture is decreased and may be associated with greater supplemental calcium doses and might increase with PTH replacement. It remains to be determined whether changes in bone remodeling and microarchitecture contribute to the effects of PTH on microfracture resistance.

Bone imaging in hypoparathyroidism.

Hypoparathyroidism (HypoPT) is an uncommon endocrine disorder characterized by chronic deficiency or absence of parathyroid hormone (PTH), which leads to a profound reduction in bone remodeling. Subjects with HypoPT typically have bone mineral densities (BMDs) by dual-energy X-ray absorptiometry (DXA) above average at all skeletal sites, with greatest scores observed at the lumbar spine. Trabecular bone score (TBS), an indirect measure of bone microarchitecture, also appears to be normal in HypoPT. By peripheral quantitative computed tomography (pQCT) of the radius, volumetric BMD at cancellous and cortical compartments, as well as cortical area and thickness, are greater in hypoparathyroid subjects than in controls. The use of high-resolution pQCT (HRpQCT) confirmed the increase in cortical volumetric BMD but demonstrated reduced cortical thickness, associated with lower cortical porosity in HypoPT. Trabeculae tend to be more numerous but thinner in hypoparathyroid subjects. It is not clear whether these structural and the dynamic skeletal abnormalities in HypoPT affect bone strength or fracture risk. Treatment of HypoPT with PTH leads to improvement in bone remodeling rate, variable changes in bone density, and a transient increase in estimated bone strength. The effect of PTH therapy on fracture risk remains unknown. This article reviews skeletal involvement and the effect of PTH treatment in patients with HypoPT, as assessed by DXA, TBS, QCT, and HRpQCT. Data on bone strength and fracture risk in HypoPT are also reviewed here.

Effects of rosiglitazone vs metformin on circulating osteoclast and osteogenic precursor cells in postmenopausal women with type 2 diabetes mellitus.

CONTEXT: Thiazolidinediones are associated with increased fractures in type 2 diabetes mellitus (T2D). One explanation is that activation of peroxisome proliferator-activated receptor-γ expression alters bone remodeling cells. OBJECTIVE: To investigate whether osteoclast and osteogenic precursor cells are altered by rosiglitazone (RSG) treatment in T2D as compared to metformin (MET) treatment. DESIGN: A randomized controlled trial of RSG or MET for 52 weeks, followed by 24 weeks of MET. SETTING: Data were generated at a tertiary care center. PATIENTS: Seventy-three T2D postmenopausal women participated. MAIN OUTCOME MEASURES: Peripheral blood mononuclear cells were isolated and cultured with receptor activator of nuclear factor κB ligand and stained for tartrate-resistant acid phosphatase to measure circulating osteoclast precursors. Peripheral blood mononuclear cells were also characterized for osteogenic, endothelial, and calcification markers by flow cytometry with the ligands osteocalcin (OCN), CD34, and CD 146. RESULTS: Tartrate-resistant acid phosphatase-positive cells increased between weeks 0 and 52 (RSG, 2.9 ± 2 to 14.0 ± 3 U/L, P = .001; MET, 3.3 ± 2 to 16.7 ± 2 U/L, P = .001), increasing further in the RSG group after changing to MET (to 26.5 ± 5 U/L, P = .05 vs wk 52). With RSG, OCN+ cells with CD34 but without CD146 fell from weeks 0 to 52 (20.1 ± 1% to 15.5 ± 2%; P = .03), remaining stable through week 76. The OCN+ cells lacking both CD34 and CD146 increased from weeks 0 to 52 (67.3 ± 2 to 74.4 ± 2%; P = .02), but returned to baseline after switching to MET. CONCLUSION: In postmenopausal women with T2D, circulating osteoclast precursor cells increase with both RSG and MET, and increase further when switching from RSG to MET. Subpopulations of cells that may be involved in the osteogenic lineage pathway are also altered with RSG. Further work is necessary to elucidate how these changes may relate to fracture risk.

Use of parathyroid hormone in hypoparathyroidism.

Hypoparathyroidism is a disorder characterized by hypocalcemia, deficient PTH, and abnormal bone remodeling. Standard treatment of hypoparathyroidism consists of oral calcium and vitamin D supplementation. However, maintaining serum calcium levels can be a challenge. In addition, concerns exist regarding hypercalciuria and ectopic calcifications that can be associated with such treatment. Hypoparathyroidism is the only classic endocrine deficiency disease for which the missing hormone, PTH, is not yet an approved treatment. This review focuses on the use of PTH in the treatment of hypoparathyroidism, in the form of teriparatide [PTH(1-34)] and the full-length molecule, PTH(1-84). Studies in hypoparathyroid subjects demonstrate that PTH(1-34) and PTH(1-84) lower or abolish supplemental calcium and vitamin D requirements as well as increase markers of bone turnover. Densitometric and histomorphometric studies in some subjects treated with PTH(1- 34) and PTH(1-84) show an improvement in bone-remodeling dynamics and return of bone metabolism toward normal levels. Given the chronic nature of hypoparathyroidism, and the expectation that PTH will be used for extended periods of time in hypoparathyroidism, further studies are needed to determine the long-term safety of PTH therapy in this population.

Circulating osteogenic precursor cells in type 2 diabetes mellitus.

CONTEXT: Type 2 diabetes mellitus (T2D) is associated with an increased risk of fractures and low bone formation. However, the mechanism for the low bone formation is not well understood. Recently, circulating osteogenic precursor (COP) cells, which contribute to bone formation, have been characterized in the peripheral circulation. OBJECTIVE: Our objective was to characterize the number and maturity of COP cells in T2D. PATIENTS, DESIGN, AND SETTING: Eighteen postmenopausal women with T2D and 27 controls participated in this cross-sectional study at a clinical research center. MAIN OUTCOME MEASURES: COP cells were characterized using flow cytometry and antibodies against osteocalcin (OCN) and early stem cell markers. Histomorphometric (n = 9) and molecular (n=14) indices of bone turnover and oxidative stress were also measured. RESULTS: The percentage of OCN(+) cells in peripheral blood mononuclear cells was lower in T2D (0.8 ± 0.2 vs. 1.6 ± 0.4%; P < 0.0001), whereas the percentage of OCN(+) cells coexpressing the early marker CD146 was increased (OCN(+)/CD146(+): 33.3 ± 7 vs. 12.0 ± 4%; P < 0.0001). Reduced histomorphometric indices of bone formation were observed in T2D subjects, including mineralizing surface (2.65 ± 1.9 vs. 7.58 ± 2.4%, P = 0.02), bone formation rate (0.01 ± 0.1 vs. 0.05 ±0.2 µm(3)/um(2) · d, P = 0.02), and osteoblast surface (1.23 ±0.9 vs. 4.60 ± 2.5%, P = 0.03). T2D subjects also had reduced molecular expression of the osteoblast regulator gene Runx2 but increased expression of the oxidative stress markers p66(Shc) and SOD2. CONCLUSIONS: Circulating OCN(+) cells were decreased in T2D, whereas OCN(+)/CD146(+) cells were increased. Histomorphometric indices of bone formation were decreased in T2D, as was molecular expression of osteoblastic activity. Stimulation of bone formation may have beneficial therapeutic skeletal consequences in T2D.

Bone structure and turnover in type 2 diabetes mellitus.

SUMMARY: We compared skeletal parameters in type 2 diabetic (T2DM) and non-diabetic postmenopausal women. Bone structure by dual energy x-ray absorptiometry (DXA) and HR-pQCT was not different, although procollagen type 1 amino-terminal propeptide (P1NP) and osteocalcin levels were lower in T2DM. INTRODUCTION: T2DM is associated with increased fracture risk, but, paradoxically, with higher cross-sectional bone density (BMD) as measured by DXA. We sought explanations to this puzzle by investigating detailed structural and biochemical skeletal parameters in T2DM. METHODS: Cross-sectional comparison of 25 postmenopausal T2DM women and 25 matched controls using DXA, high-resolution peripheral quantitative computed tomography (HR-pQCT) and biochemical bone turnover markers. RESULTS: BMD by DXA did not differ between T2DM and controls. HR-pQCT assessment also did not differ, with the exception of cortical area at the tibia, which tended to be lower in the diabetics (difference of 12 ± 6 [mean ± SD] mm, p = 0.06). P1NP and osteocalcin levels were lower in T2DM as compared to controls (P1NP, 34.3 ± 16 vs. 57.3 ± 28 ng/ml; p = 0.005; osteocalcin, 4.5 ± 2 vs. 6.2 ± 2 nmol/L; p = 0.001). CONCLUSIONS: Postmenopausal women with T2DM had lower levels of bone formation markers as compared to controls. Aside from a possible decrease in cortical bone area at a weight-bearing site, bone structure was not altered in T2DM. Lower bone turnover may be a skeletal parameter that is present in T2DM.

Parathyroid hormone stimulates circulating osteogenic cells in hypoparathyroidism.

CONTEXT: The osteoanabolic properties of PTH may be due to increases in the number and maturity of circulating osteogenic cells. Hypoparathyroidism is a useful clinical model because this hypothesis can be tested by administering PTH. OBJECTIVE: The objective of the study was to characterize circulating osteogenic cells in hypoparathyroid subjects during 12 months of PTH (1-84) administration. DESIGN: Osteogenic cells were characterized using flow cytometry and antibodies against osteocalcin, an osteoblast-specific protein product, and stem cell markers CD34 and CD146. Changes in bone formation from biochemical markers and quadruple-labeled transiliac crest bone biopsies (0 and 3 month time points) were correlated with measurements of circulating osteogenic cells. SETTING: The study was conducted at a clinical research center. PATIENTS: Nineteen control and 19 hypoparathyroid patients were included in the study. INTERVENTION: Intervention included the administration of PTH (1-84). RESULTS: Osteocalcin-positive cells were lower in hypoparathyroid subjects than controls (0.7 ± 0.1 vs. 2.0 ± 0.1%; P < 0.0001), with greater coexpression of the early cell markers CD34 and CD146 among the osteocalcin-positive cells in the hypoparathyroid subjects (11.0 ± 1.0 vs. 5.6 ± 0.7%; P < 0.001). With PTH (1-84) administration, the number of osteogenic cells increased 3-fold (P < 0.0001), whereas the coexpression of the early cell markers CD34 and CD146 decreased. Increases in osteogenic cells correlated with circulating and histomorphometric indices of osteoblast function: N-terminal propeptide of type I procollagen (R(2) = 0.4, P ≤ 0.001), bone-specific alkaline phosphatase (R(2) = 0.3, P < 0.001), osteocalcin (R(2) = 0.4, P < 0.001), mineralized perimeter (R(2) = 0.5, P < 0.001), mineral apposition rate (R(2) = 0.4, P = 0.003), and bone formation rate (R(2) = 0.5, P < 0.001). CONCLUSIONS: It is likely that PTH stimulates bone formation by stimulating osteoblast development and maturation. Correlations between circulating osteogenic cells and histomorphometric indices of bone formation establish that osteoblast activity is being identified by this methodology.

Therapy of hypoparathyroidism with intact parathyroid hormone.

UNLABELLED: Hypoparathyroidism, a disorder characterized by low parathyroid hormone (PTH), is generally treated with oral calcium and vitamin D supplementation. We investigated the effects of PTH(1-84) treatment in 30 hypoparathyroid subjects for 24 months. PTH(1-84) treatment in hypoparathyroidism significantly reduced supplemental calcium and 1,25-dihydroxyvitamin D requirements without generally altering serum and urinary calcium levels. INTRODUCTION: Hypoparathyroidism, a disorder characterized by low PTH, is associated with hypocalcemia, hypercalciuria, and increased bone mineral density (BMD). Conventional therapy with calcium and 1,25-dihydroxyvitamin D can maintain the serum calcium concentration, but doses are high, and control is variable. We investigated the effects of human PTH(1-84) treatment in hypoparathyroidism. METHODS: Thirty subjects with hypoparathyroidism were treated in an open-label study of PTH(1-84) 100 µg every other day by subcutaneous injection for 24 months, with monitoring of calcium and vitamin D supplementation requirements, serum and 24 h urinary calcium excretion, and BMD by dual energy X-ray absorptiometry. RESULTS: Requirements for supplemental calcium decreased significantly (3,030±2,325 to 1,661±1,267 mg/day (mean±SD); p<0.05), as did requirements for supplemental 1,25-dihydroxyvitamin D (0.68±0.5 to 0.40±0.5 µg/day; p<0.05). Serum calcium levels and 24 h urinary calcium excretion were mostly unchanged at 24 months. BMD increased at the lumbar spine by 2.9±4% from baseline (p<0.05), while femoral neck BMD remained unchanged and distal one third radial BMD decreased by 2.4±4% (p<0.05). CONCLUSION: PTH(1-84) treatment in hypoparathyroidism significantly reduces supplemental calcium and 1,25-dihydroxyvitamin D requirements without generally altering serum and urinary calcium levels.

Assessment of trabecular and cortical architecture and mechanical competence of bone by high-resolution peripheral computed tomography: comparison with transiliac bone biopsy.

UNLABELLED: We compared microarchitecture and mechanical competence parameters measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite-element analysis of radius and tibia to those measured by histomorphometry, micro-CT, and finite-element analysis of transiliac bone biopsies. Correlations were weak to moderate between parameters measured on biopsies and scans. INTRODUCTION: HR-pQCT is a new imaging technique that assesses trabecular and cortical bone microarchitecture of the radius and tibia in vivo. The purpose of this study was to determine the extent to which microarchitectural variables measured by HR-pQCT reflect those measured by the "gold standard," transiliac bone biopsy. METHODS: HR-pQCT scans (Xtreme CT, Scanco Medical AG) and iliac crest bone biopsies were performed in 54 subjects (aged 39 +/- 10 years). Biopsies were analyzed by 2D quantitative histomorphometry and 3D microcomputed tomography (microCT). Apparent Young's modulus, an estimate of mechanical competence or strength, was determined by micro-finite-element analysis (microFE) of biopsy microCT and HR-pQCT images. RESULTS: The strongest correlations observed were between trabecular parameters (bone volume fraction, number, separation) measured by microCT of biopsies and HR-pQCT of the radius (R 0.365-0.522; P < 0.01). Cortical width of biopsies correlated with cortical thickness by HR-pQCT, but only at the tibia (R = 0.360, P < 0.01). Apparent Young's modulus calculated by microFE of biopsies correlated with that calculated for both radius (R = 0.442; P < 0.001) and tibia (R = 0.380; P < 0.001) HR-pQCT scans. CONCLUSIONS: The associations between peripheral (HR-pQCT) and axial (transiliac biopsy) measures of microarchitecture and estimated mechanical competence are significant but modest.

Diagnosis of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop.

OBJECTIVE: Asymptomatic primary hyperparathyroidism (PHPT) is a common clinical problem. The purpose of this report is to guide the use of diagnostic tests for this condition in clinical practice. PARTICIPANTS: Interested professional societies selected a representative for the consensus committee and provided funding for a one-day meeting. A subgroup of this committee set the program and developed key questions for review. Consensus was established at a closed meeting that followed. The conclusions were then circulated to the participating professional societies. EVIDENCE: Each question was addressed by a relevant literature search (on PubMed), and the data were presented for discussion at the group meeting. CONSENSUS PROCESS: Consensus was achieved by a group meeting. Statements were prepared by all authors, with comments relating to accuracy from the diagnosis subgroup and by representatives from the participating professional societies. CONCLUSIONS: We conclude that: 1) reference ranges should be established for serum PTH in vitamin D-replete healthy individuals; 2) second- and third-generation PTH assays are both helpful in the diagnosis of PHPT; 3) DNA sequence testing can be useful in familial hyperparathyroidism or hypercalcemia; 4) normocalcemic PHPT is a variant of the more common presentation of PHPT with hypercalcemia; 5) serum 25-hydroxyvitamin D levels should be measured and, if vitamin D insufficiency is present, it should be treated as part of any management course; and 6) the estimated glomerular filtration rate should be used to determine the level of kidney function in PHPT: an estimated glomerular filtration rate of less than 60 ml/min.1.73 m2 should be a benchmark for decisions about surgery in established asymptomatic PHPT.

Hormonal responses to a 160-km race across frozen Alaska.

BACKGROUND: Severe physical and environmental stress seems to have a suppressive effect on the hypothalamic-pituitary-gonadal (HPG) axis in men. Examining hormonal responses to an extreme 160-km competition across frozen Alaska provides a unique opportunity to study this intense stress. OBJECTIVE: To examine hormonal responses to an ultra-endurance race. METHODS: Blood samples were obtained from 16 men before and after racing and analyzed for testosterone, interleukin-6 (IL-6), growth hormone (GH) and cortisol. Six subjects (mean (SD) age 42 (7) years; body mass 78.9 (7.1) kg; height 1.78 (0.05) m raced by bicycle (cyclists) and 10 subjects (age 35 (9) years; body mass 77.9 (10.6) kg; height, 1.82 (0.05) m) raced by foot (runners). Mean (SD) finish times were 21.83 (6.27) and 33.98 (6.12) h, respectively. RESULTS: In cyclists there were significant (p< or =0.05) mean (SD) pre-race to post-race increases in cortisol (254.83 (135.26) to 535.99 (232.22) nmol/l), GH (0.12 (0.23) to 3.21 (3.33) microg/ml) and IL-6 (2.36 (0.42) to 10.15 (3.28) pg/ml), and a significant decrease in testosterone (13.81 (3.19) to 5.59 (3.74) nmol/l). Similarly, in runners there were significant pre-race to post-race increases in cortisol (142.09 (50.74) to 452.21 (163.40) ng/ml), GH (0.12 (0.23) to 3.21 (3.33) microg/ml) and IL-6 (2.42 (0.68) to 12.25 (1.78) pg/ml), and a significant decrease in testosterone (12.32 (4.47) to 6.96 (3.19) nmol/l). There were no significant differences in the hormonal levels between cyclists and runners (p>0.05). CONCLUSIONS: These data suggest a suppression of the hypopituitary-gonadal axis potentially mediated by amplification of adrenal stress responses to such an ultra-endurance race in environmentally stressful conditions.

The influence of porosity on the integration histology of two polypropylene meshes for the treatment of abdominal wall defects in dogs.

Two types of monofilament polypropylene mesh with different pore sizes, mass densities and burst strengths were used to repair two identical paired full-thickness abdominal wall defects in ten dogs, in order to compare their integration histology 90 days after implantation. On one side a standard mesh, Prolene (Ethicon), was sutured to the borders of the defect, while on the other a new ultralightweight macroporous mesh, Mpathy mesh, was used. There was a significantly greater densitometric proportion of mature (type I) collagen (58.38%) for Mpathy mesh compared to Prolene (34.05%, P=0.01). Although Prolene has 3.6 times the burst strength of Mpathy mesh, the implanted tissue strength was marginally greater for Mpathy mesh. We conclude that Mpathy mesh gives a surgical repair that is at least as strong as that provided by Prolene, along with a higher concentration of mature collagen and less fibrosis (P=0.07), in this canine histology model.

Cinacalcet hydrochloride reduces the serum calcium concentration in inoperable parathyroid carcinoma.

BACKGROUND: Management of inoperable parathyroid carcinoma presents a challenge because until recently, effective medical therapy was not available. Morbidity and mortality result primarily from severe hypercalcemia. We assessed the ability of the calcimimetic cinacalcet HCl to reduce serum calcium in patients with parathyroid carcinoma as well as its effect on PTH concentrations, bone turnover markers, safety, and health-related quality of life variables. METHODS: Twenty-nine patients with parathyroid carcinoma were enrolled in this open-label, single-arm study consisting of titration and maintenance phases. Cinacalcet doses were titrated (30 mg twice daily to 90 mg four times daily) for 16 wk or until serum calcium was no more than 10.0 mg/dl. The study endpoint was the proportion of patients with at least a 1 mg/dl reduction in serum calcium at the end of the titration phase (responders). RESULTS: Mean (+/- se) serum calcium (14.1 +/- 0.4 mg/dl) and PTH (697 +/- 94 pg/ml) were markedly elevated at baseline. At the end of the titration period, serum calcium was reduced by at least 1 mg/dl in 62% of patients (mean decline to 12.4 +/- 0.5 mg/dl). In the 18 responders, serum calcium fell from 15.0 +/- 0.5 to 11.2 +/- 0.3 mg/dl (P < 0.001). The greatest reductions in serum calcium were observed in patients with highest baseline calcium levels. PTH levels decreased, but not significantly, to 635 +/- 73 pg/ml (-4.6%). Adverse events included nausea, vomiting, headache, and fracture. CONCLUSIONS: Cinacalcet effectively reduces hypercalcemia in approximately two thirds of patients with inoperable parathyroid carcinoma and may represent an important new treatment option for these patients.

Normocalcemic primary hyperparathyroidism: further characterization of a new clinical phenotype.

CONTEXT: Patients with elevated PTH and consistently normal serum calcium levels, in whom secondary causes of hyperparathyroidism have been excluded, may represent the earliest presentation of primary hyperparathyroidism (PHPT). OBJECTIVE: The objective of the study was to characterize patients with normocalcemic PHPT referred to a bone disease unit. DESIGN: This was a longitudinal cohort study. SETTING: Ambulatory patients were referred to the metabolic bone disease unit. PATIENTS: The study population included 37 patients [aged 58 yr, range 32-78; 95% female; serum calcium, 9.4 +/- 0.1 (sem) mg/dl (2.3 +/- 0.02 mmol/liter), reference range, 8.5-10.4 (2.1-2.6 mmol/liter); PTH, 93 +/- 5 pg/ml]. INTERVENTIONS: Interventions included yearly (median 3 yr; range 1-8 yr) physical examination, biochemical indices, and bone mineral density (BMD). MAIN OUTCOME MEASURES: We measured the development of features of PHPT. RESULTS: Evaluation for classical features of PHPT revealed a history of kidney stones in five (14%), fragility fractures in four (11%), and osteoporosis in 57% [spine (34%), hip (38%), and/or distal one third radius (28%)]. BMD did not show preferential bone loss at the distal one third radius (T scores: spine, -2.00 +/- 0.25; hip, -1.84 +/- 0.18; one third radius, -1.74 +/- 0.22). Further signs of PHPT developed in 40% (seven hypercalcemia; one kidney stone; one fracture; two marked hypercalciuria; six had >10% BMD loss at one or more site(s) including four patients developing World Health Organization criteria for osteoporosis). Seven patients (three hypercalcemic, four persistently normocalcemic) underwent successful parathyroidectomy. CONCLUSIONS: Patients seen in a referral center with normocalcemic hyperparathyroidism have more substantial skeletal involvement than is typical in PHPT and develop more features and complications over time. These patients may represent the earliest form of symptomatic, rather than asymptomatic, PHPT.

Parathyroid hormone as an anabolic therapy for women and men.

The quest for effective treatment of osteoporosis merits great attention because of the widespread, worldwide prevalence of this disease. Antiresorptive drugs reduce bone turnover, increase bone density and improve other aspects of bone quality. This article concentrates on another approach, namely the use of anabolic therapy in which the prospects for improving bone quality are even greater. Parathyroid hormone is available as the aminoterminal fragment, PTH(1-34), known as teriparatide, and is being studied in its full-length form, PTH(1-84). Teriparatide improves bone quality by actions on bone turnover, bone density, bone size and microarchitecture. In women, teriparatide reduces both vertebral and non-vertebral fractures. In individuals who have been treated previously with an antiresorptive agent, the ability of PTH to increase bone density may be reduced. Combination therapy with teriparatide or PTH(1-84) and an antiresorptive does not appear, at this time, to offer advantages over the use of parathyroid hormone alone. In order to maintain the densitometric gains in bone density with parathyroid hormone, it is important to follow its use with an antiresorptive agent.

Influence of muscle strength and total work on exercise-induced plasma growth hormone isoforms in women.

The purpose of this investigation was to determine the influence of physical strength and the ability to do more total work on human growth hormone (GH) variants to a heavy resistance exercise protocol in untrained women. From a distribution of 100 healthy, untrained women, the strongest 10 women (S) and the weakest 10 women (W) were compared for GH responses pre- and post an acute heavy resistance exercise test (AHRET, 6 sets of 10 RM squats, 2 minutes rest between sets). Blood samples were obtained pre-exercise and immediately post-exercise and subsequently analysed in total as well as fractionated by Sephacryl S-100R column chromatography into three molecular weight size classes: fraction A: > 60 kD, fraction B: 30-60 kD, fraction C: < 30 kD. For each total sample as well as each fraction, immunoreactive GH was measured via the Nichols IRMA, while bioactive GH was measured via the hypox rat tibial line bioassay and Diagnostic Systems Laboratory's immunofunctional GH ELISA. No exercise-induced changes or differences between groups were observed in the tibial line bioassay. However, the S group displayed a significantly higher pre-exercise resting value in the total fraction than the W group. Conversely, the W group exhibited a significantly higher pre-exercise value in the smaller molecular weight fraction C. With regards to the immunofunctional and immunoreactive assays, the total fraction, fraction A, and fraction B demonstrated significant (P < or = 0.05) exercise-induced increases in both the S and W group despite no group differences. For the Nichols and immunofunctional assays significant exercise-induced changes were observed in the smaller molecular weight C fraction in the W group but not the S group. However, the S group displayed a significantly higher pre-exercise value in fraction C relative to the W group. These data demonstrate for the first time that differences exist in the GH molecular weight variants between strong and weak untrained women, with the lower molecular weight variants seemingly less responsive to greater amounts of exercise in stronger women, thus suggesting differential regulation of GH molecular weight variants during resistance exercise due to pre-existing physical parameters.

Safety measures of L-carnitine L-tartrate supplementation in healthy men.

The purpose of this investigation was to examine the effects of ingestion of L-CARNIPURE (L-carnitine L-tartrate [LCLT]) on alterations in a complete blood cell profile and in circulating metabolic enzymes. Using a balanced, placebo (P), cross-over design (1 week washout), 10 healthy, active men volunteered and acted as their own control taking either a P or LCLT supplement (3 g.day(-1)) for 3 weeks. Postabsorptive morning blood samples were obtained both before and after 21 days of P and LCLT supplementation. Serum samples were analyzed for clinical chemistries including a complete chemistry panel with markers of liver and renal function along with various minerals and electrolytes. In addition, whole blood was analyzed for a complete blood count with differential. It was determined that there were no statistically significant differences between the LCLT and the placebo conditions for any of the variables examined. The results of this study suggest that LCLT, when used as a dietary supplement, has no adverse effects on metabolic and hematological safety variables in normally healthy men.

Physiological and performance responses to tournament wrestling.

PURPOSE: The purpose of this study was to investigate the physiological and performance responses to a simulated freestyle wrestling tournament after typical weight loss techniques used by amateur wrestlers. METHODS: Twelve Division I collegiate wrestlers (mean +/- SD;19.33 +/- 1.16 yr) lost 6% of total body weight during the week before a simulated, 2-d freestyle wrestling tournament. A battery of tests was performed at baseline and before and immediately after each individual match of the tournament. The test battery included assessment for body composition, reaction/movement time, lower and upper body power and isokinetic strength, and a venous blood sample. RESULTS: Lower body power and upper body isometric strength were significantly reduced as the tournament progressed (P < or = 0.05). Significant elevations in testosterone, cortisol, and lactate were observed after each match (P < or = 0.05). However, there was a significant reduction (P < or = 0.05) in resting testosterone values in the later matches. Norepinephrine increased significantly (P < or = 0.05) after each match, whereas epinephrine increased significantly (P < or = 0.05) after each match except the last match of each day. Plasma osmolality was consistently higher than normal values at all times including baseline, with significant increases observed after each match (P < or = 0.05). CONCLUSIONS: Tournament wrestling augments the physiological and performance decrements of weight loss and its impact is progressive over 2 d of competition. The combined effects of these stresses may ultimately be reflected in a wrestler's ability to maintain physical performance throughout a tournament.