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The Journal of Clinical Endocrinology & Metabolism Vol. 82, No. 8 2548-2551
Copyright © 1997 by The Endocrine Society

Experimental Studies

Hemodynamic Effects of Parathyroid Hormone-Related Peptide-(1–34) in Humans1

Michael Wolzt, Leopold Schmetterer, Guido Dorner, Georg Zelger, Jesusa Entlicher, Stylianos Kapiotis and Hans-Georg Eichler

Department of Clinical Pharmacology (M.W., L.S., G.D., G.Z., J.E., H.-G.E.), the Institute of Medical Physics (L.S.), and the Department of Medical and Chemical Laboratory Diagnostics (S.K.), Vienna University, Vienna, Austria

Address all correspondence and requests for reprints to: Dr. Michael Wolzt, Klinische Pharmakologie, Allgemeines Krankenhaus Wien, Währingergürtel 18–20, A-1090 Vienna, Austria.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
It has been suggested that PTH-related peptide-(1–34) (PTHrP) is a regulator or modulator of regional or systemic cardiovascular function with varying vasodilating actions in different species. We have studied the cardiovascular pharmacodynamic profile of PTHrP in healthy humans.

In a double blind, placebo-controlled, cross-over study design, eight healthy subjects were assigned to stepwise increased iv doses of PTHrP. In addition, a dose-response curve to PTHrP was constructed in a dorsal hand vein in eight subjects.

PTHrP dose-dependently increased pulse rate and renal plasma flow by more than 50% (P < 0.0001 for both parameters, by ANOVA), but only a small venodilating response was seen in hand vein experiments, and no effect was noted on mean arterial blood pressure or cardiac inotropic performance.

Although it is unlikely that PTHrP regulates systemic hemodynamics, its chronotropic effect and its potent action on renal plasma flow may represent the primary cardiovascular physiological targets of action.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
PTH-RELATED peptide-(1–34) (PTHrP) was originally identified from tumors associated with hypercalcemia (1). The recent characterization of PTHrP-like immunoreactivity in normal tissue suggests a physiological cardiovascular function; PTHrP is expressed in normal fetal and adult heart tissues (2) and in large vessels (3). PTHrP expression in several types of smooth muscle is stimulated by endothelin, norepinephrine, and thrombin (4) and by cyclic stretch (5) and angiotensin II (6) in a synergistic manner.

Several animal studies have suggested that the potent vasodilator PTHrP is a regulator or modulator of regional or systemic cardiovascular function (7, 8, 9, 10, 11), but these results have not been confirmed in humans in vivo until now. In man, no cardiovascular effects of PTHrP were observed at doses that affected total serum calcium and 1,25-dihydroxycholecalciferol and urinary phosphate levels (12). In contrast to the scenario in humoral hypercalcemia of malignancy, where PTHrP plays a pathophysiological role, the complex physiological cardiovascular functions of PTHrP are less well understood (13).

In an effort to enhance our understanding of the physiological role in humans in vivo, the systemic and regional hemodynamic effects of PTHrP were studied in healthy subjects employing well characterized, noninvasive methods.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Study population and design

After approval of the study protocol by the ethics committee of Vienna University School of Medicine and after written informed consent was obtained, 16 healthy, nonsmoking, drug-free male volunteers between 21–34 yr of age were studied. The study was performed in accordance with the Declaration of Helsinki and European Community Guidelines for Good Clinical Practice. Each subject passed a screening examination that included history and physical examination, 12-lead electrocardiogram, complete blood cell count with differential, urinalysis, urine drug screen, serum electrolytes, bilirubin, blood urea nitrogen, creatinine, cholesterol, triglycerides, {gamma}-glutamyltransferase, glucose, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, total protein, activated partial thromboplastin time, thrombin time, hepatitis A, B, and C serological tests, and human immunodeficiency virus antibody tests.

Study protocol

The hemodynamic effects of PTHrP [PTHrP-(1–34), Clinalfa, Laufelfingen, Switzerland] were studied in two different study cohorts. Glass syringes and short tubing systems were used for PTHrP infusion experiments to avoid adhesion of the peptides. All subjects were asked to refrain from alcohol and caffeine for at least 12 h before study days. Studies were performed in a quiet room with an ambient temperature of 22 C that had complete resuscitation facilities.

Hand vein compliance studies

In an open label study design, a dose-response curve for PTHrP was constructed in appropriate dorsal hand veins of eight subjects (24.5 ± 2.6 yr, mean ± SD) with body weights between 70–93 kg (79.8 ± 7.4 kg). The method was previously described in detail (14, 15). Briefly, a needle was inserted into a suitable dorsal hand vein of the supine subjects, and a continuous infusion (0.31 mL/min) of physiological saline was started. A linear variable differential transformer (LVDT; model 100 MHR, Schaevitz Engineering, Pennsauken, NJ) was mounted on the hand, and the freely movable core of the LVDT was placed on the apex of the vein under study. Inflation of a sphygmomanometer cuff on the same arm to 45 mm Hg resulted in a change in diameter of the vein, movement of the core, and voltage output, which was recorded on a strip chart recorder. The baseline venodilatation during saline infusion with the cuff inflated was defined as 100% relaxation (or 0% constriction); the recording obtained with the cuff not inflated and the vein emptied was defined as 100% constriction. All local infusions of PTHrP lasted at least 6 min; the cuff was inflated for at least 2 min at intervals during each infusion period to ensure that the signal from the LVDT had plateaued. Increasing concentrations of PTHrP were infused in a sequential manner (2- to 3-fold dose increments); the infusion rate was kept constant at 0.31 mL/min.

There is little or no venous tone in superficial hand veins in a warm and relaxed subject (16); therefore, the effects of venodilating agents cannot be directly assessed. However, a dose-response relationship for venodilating substances can be studied when the studied vein is preconstricted to about 80% of the maximal constriction. The venodilating effect of PTHrP was, therefore, evaluated during continuous infusion of a constant preconstriction dose of phenylephrine (Neo-Synephrine, Winthrop-Breon Laboratories, New York, NY), an {alpha}1-adrenoceptor agonist, and simultaneous infusion of increasing concentrations of PTHrP (0.015–57.9 pmol/min). Assuming that blood flow in the hand vein under study is negligible during cuff inflation, the local concentration of PTHrP rises to a maximum of approximately 174 pmol PTHrP during a 3-min venous stasis period. Previous results showed that constriction with phenylephrine is constant during at least 80 min (17). The venous diameter at this preconstriction dose was taken as the new baseline (0% relaxation) for the dose-response curve. Coinfusion experiments were stopped after administration of the highest dose of PTHrP.

Additional experiments were conducted to study the potential for tachyphylaxis to PTHrP. A constant dose of PTHrP that produced a clear-cut dilation of the phenylephrine-preconstricted vein was coinfused with the preconstriction dose of phenylephrine for 60 min (n = 3). The diameter of the preconstricted vein was measured every 8 min.

Studies of systemic hemodynamic effects

The study was conducted in a double blind, randomized, two-way cross-over design, with a washout period between study days of at least 5 days. Eight subjects (mean ± SD, 30.0 ± 3.5 yr) with body weights between 63–95 kg (78.3 ± 9.5 kg) were assigned to receive stepwise increased doses of PTHrP [0 (saline), 0.9, 1.9, 3.7, 7.5, and 14.9 nmol/min] or placebo in a balanced sequence. The highest dose selected corresponded to a dose of 157–237 pmol PTHrP/kg·min. Each stepwise infusion period lasted 15 min unless an increase of more than 40 mm Hg or a decrease of more than 20 mm Hg in mean arterial pressure, or an increase of more than 40 or a decrease of more than 20 beats/min (bpm) in pulse rate vs. those during the baseline infusion period, or any systemic effects, e.g. palpitation, headache, or dizziness, occurred. To maintain double blind conditions, six numbered syringes containing physiological saline solution were prepared and infused sequentially. All recordings and venous blood sampling were performed during the last 5 min of each infusion step. Throughout the infusion periods, subjects were in a supine position. On the second trial day, subjects crossed over to the alternate treatment.

To standardize the sodium balance, all subjects received 3 g/day sodium chloride for 3 days before the trial days in addition to the usual salt intake. Subjects were asked to drink 300 mL water/h during hemodynamic studies.

For estimation of renal plasma flow (RPF), all subjects received primed constant infusions of para-aminohippurate (PAH) on both trial days, starting 45 min before PTHrP or placebo treatment. After an iv loading dose of PAH (Clinalfa, Laufelfingen, Switzerland; 8 mg/kg), a continuous infusion of PAH to attain a plasma concentration of 0.02 mg/mL at an estimated PAH clearance of 750 mL/min·1.73 m-2 was started. This method has been validated previously (18). It is well known that within a short period of time, steady state levels of PAH may not be achieved. An appropriate infusion regimen and a placebo control group were, therefore, selected to detect clinically relevant changes in PAH clearance (19, 20).

For determination of plasma levels of total and ionized calcium, phosphate, 1,25-dihydroxycholecalciferol [1,25-(OH)2D3], and PAH, venous blood was collected from iv cannulas at the end of each drug infusion period into appropriate tubes. The tubes for quantification of 1,25-(OH)2D3 and PAH were centrifuged at 1500 x g for 10 min. The clear supernatant was removed, frozen, and stored at -20 C until assayed.

Systolic time intervals

The duration of phases of the left ventricular systole was measured from simultaneous recordings of the electrocardiogram (lead II, which most clearly demonstrated the onset of ventricular depolarization) and the phonocardiogram (from the third left intercostal space). The registrations were obtained in end-expiratory apnea. Five RR complexes of the jet-recorded strip (Mingograph 410, Siemens, Erlangen, Germany) were averaged by an experienced observer to calculate total electromechanical systole from the onset of ventricular depolarization to the onset of the high frequency vibrations of the aortic component of the second heart sound. Correction for the individual heart rate was made using a regression equation as suggested by Weissler et al. (21). The standard approach used is a well established noninvasive method to assess within-subject changes in cardiovascular performance (22) and has been used to characterize drug-induced inotropic effects (23).

Noninvasive systemic hemodynamics

Mean arterial blood pressure was measured in the upper arm by an automated oscillometric device (HP CMS-patient monitor, Hewlett-Packard, Palo Alto, CA). The pulse rate was recorded automatically using a finger pulse oxymetric device (HP CMS-patient monitor). The sensitivity of these methods has been reported previously (23).

Analytical methods

The plasma PAH concentration was measured by photometric analysis (24). RPF was estimated by the plasma clearance of PAH (18). Total and ionized calcium, phosphate, and 1,25-(OH)2D3 concentrations were determined using routine laboratory methods.

Data analysis

All statistical analyses were performed using the Statistica software package (release 4.5, StatSoft, Tulsa, OK). Individual dose-response curves from hand vein compliance studies were analyzed with a sigmoid maximal response model and the computer program Origin (Release 3.5, Microcal Software, Northampton, MA). This iterative, nonlinear curve-fitting program estimates the dose that produces a half-maximal response (ED50). ED50 values were based on doses at 50% of an individual’s maximal effect (Emax). The Emax values were expressed as a percentage of maximum relaxation. The effects of PTHrP on outcome variables were assessed by repeated measure ANOVA. A two-tailed P < 0.05 was considered significant.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Hand vein compliance studies

The local infusions of PTHrP caused a dose-dependent dilation of the phenylephrine-preconstricted vein in all subjects, with an Emax of 39 ± 20% relaxation (mean ± SD; range, 11–73% relaxation). There was a considerable intersubject variability in sensitivity to PTHrP, resulting in a range of ED50 values from 0.2–8.9 pmol PTHrP/min (mean ± SD, 1.9 ± 3.2 pmol PTHrP/min). No tachyphylaxis was observed during a 60-min perfusion period of a constant venodilating dose of PTHrP.

Systemic hemodynamic effects

No significant differences between treatment groups were observed at baseline (Table 1Go). PTHrP infusions had to be discontinued in two subjects at 7.5 nmol/min and in three subjects at 14.9 nmol/min due to flush, tachycardia, dizziness, and nausea. In these subjects, mean arterial pressure and pulse rate changed from 93 ± 11 mm Hg (mean ± SD) and 86 ± 18 bpm at the end of the preceding dose level to 87 ± 16 mm Hg and 90 ± 18 bpm at drug discontinuation and to 96 ± 12 mm Hg and 77 bpm 5 min after the PTHrP infusion. All adverse events were classified as mild in intensity, and no subject required specific treatment.


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  		Table 1. Baseline hemodynamic parameters

 
Dose-response relationships for individual parameters are illustrated in Fig. 1Go. Infusions of PTHrP markedly increased pulse rate and renal plasma flow, but did not affect the other hemodynamic parameters under study. The hemodynamic effects were statistically significant vs. baseline and vs. placebo at 0.9 nmol/min (P < 0.0001 for both parameters, by ANOVA) and were still detectable 15 min after the drug infusion series.



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  		Figure 1. Dose-response relationship for PTHrP on hemodynamic parameters in eight healthy subjects with a mean body weight of 78.3 ± 9.5 kg. Line plots show hemodynamic effects as a percentage of the baseline during continuous iv infusion of placebo (line with no symbols) and of 0, 0.9, 1.9, 3.7, 7.5, and 14.9 nmol/min PTHrP (line with solid circles) and 15 min after the infusion series. The infusion series was applied with steps of 15 min each and had to be discontinued in five subjects prematurely due to systemic side-effects. The results at 7.5 and 14.9 nmol PTHrP/min, which correspond to 157–237 pmol PTHrP/kg·min at the highest dose administered, are calculated from six and three subjects, respectively (open circles). Results are presented as the mean ± sd. *, P < 0.0001 vs. baseline and placebo, by ANOVA. QS2c, Total electromechanical systole, corrected for heart rate.

 
The short term infusion of PTHrP did not influence total and ionized serum calcium, phosphate, or 1,25-(OH)2D3 levels (Table 2Go).


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  		Table 2. Effect of PTHrP or placebo administration on serum levels of calcium (Ca), ionized calcium (Ca2+), phosphate (Ph), and 1,25-(OH)2 D3

 

   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
This study confirms animal experiments and highlights the potential physiological hemodynamic role of PTHrP in humans in vivo. Whereas pulse rate and RPF increased by more than 50%, no effect was noted on mean arterial blood pressure or parameters of cardiac inotropic performance. Based on the side-effect profile of PTHrP, it could be suggested that hypotensive effects might have occurred if the subjects were standing, which argues in favor of a clinically relevant venodilating action. However, only a small venodilating response was seen in hand vein experiments. The rapid onset of action after iv administration of pharmacological doses of PTHrP, previously observed in animal studies (7), was seen by the sudden onset of the side-effects of PTHrP that necessitated discontinuation of drug administration in five subjects. This may also explain why the increase in pulse rate was slightly smaller at 14.9 than at 7.5 nmol PTHrP/min, because only three subjects, who were presumably less sensitive to PTHrP, completed the higher dose stage. Interestingly, the hemodynamic effects of PTHrP were still detectable 15 min after the end of drug treatment, which is approximately two half-lives of PTHrP in blood (25).

It has been suggested from experiments in isolated hearts that the cardiac inotropic actions of PTHrP (8) are secondary effects of increased coronary flow and heart rate (26). This concept is in agreement with our noninvasive in vivo results, where positive chronotropic, but no inotropic, effects were observed. However, it has to be noted that our results from indirect measurement techniques may have been limited by confounding cardiovascular reflex responses. Although we cannot rule out that PTHrP may exert a profound hypotensive response or additional hemodynamic responses at higher doses, our results, nevertheless, indicate that the venous vascular sensitivity and the responsiveness of resistance vessels to PTHrP are comparably small. In contrast, the renal vasculature was highly sensitive to PTHrP, which is in agreement with animal experiments (11, 27, 28, 29). The potent vasodilating actions of PTHrP on the renal vasculature may have therapeutic value and deserve further study.

Infusions of PTHrP had no effect on calcium, ionized calcium, or serum 1,25-(OH)2D3 concentrations. Previous studies indicate that biochemical responses to exogenous PTHrP are seen 2 h after continuous drug administration (12, 30). It is, therefore, likely that the lack of a biochemical effect of PTHrP in our experiments is attributable to the short duration of drug infusion.

In conclusion, our results with short term infusions of pharmacological doses of PTHrP in humans demonstrate the potential physiological functions of PTHrP in the vascular system. Whereas it has to be considered unlikely that PTHrP regulates systemic hemodynamics, its chronotropic effect and its potent action on RPF may represent the primary cardiovascular physiological targets of action and may be used for future therapeutic approaches in patients with renal impairment.


   Footnotes
 
1 This work was supported by a grant from the Fonds zur Förderung der Wissenschaftlichen Forschung (Grant P11436-MED). Back

Received January 31, 1997.

Revised April 23, 1997.

Accepted May 1, 1997.


   References
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 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Martin TJ, Allan EH, Caple IW, et al. 1989 Parathyroid hormone-related protein: isolation, molecular cloning, and mechanism of action. Recent Prog Horm Res. 45:467–502.
  2. Bui TD, Shallal A, Malik AN, et al. 1993 Parathyroid hormone related peptide gene expression in human fetal and adult heart. Cardiovasc Res. 27:1204–1208.[Free Full Text]
  3. Burton DW, Brandt DW, Deftos LJ. 1994 Parathyroid hormone-related protein in the cardiovascular system. Endocrinology. 135:253–261.[Abstract]
  4. Hongo T, Kupfer J, Enomoto H, et al. 1991 Abundant expression of parathyroid hormone-related protein in primary rat aortic smooth muscle cells accompanies serum-induced proliferation. J Clin Invest. 88:1841–1847.
  5. Noda M, Takuwa Y, Katoh T, Kurokawa K. 1996 Mechanical force regulation of vascular parathyroid hormone-related peptide expression. Kidney Int. 55(Suppl):S154–S155.
  6. Noda M, Katoh T, Takuwa N, Kumada M, Kurokawa K, Takuwa Y. 1994 Synergistic stimulation of parathyroid hormone-related peptide gene expression by mechanical stretch and angiotensin II in rat aortic smooth muscle cells. J Biol Chem. 269:17911–17917.[Abstract/Free Full Text]
  7. Nickols GA, Nana AD, Nickols MA, DiPette DJ, Asimakis GK. 1989 Hypotension and cardiac stimulation due to the parathyroid hormone-related protein, humoral hypercalcemia of malignancy factor. Endocrinology. 125:834–841.[Abstract]
  8. Roca-Cusachs A, DiPette DJ, Nickols GA. 1991 Regional and systemic hemodynamic effects of parathyroid hormone-related protein: preservation of cardiac function and coronary and renal flow with reduced blood pressure. J Pharmacol Exp Ther. 256:110–118.[Abstract/Free Full Text]
  9. Shan J, Pang PK, Lin HC, Yang MC. 1994 Cardiovascular effects of human parathyroid hormone and parathyroid hormone-related peptide. J Cardiovasc Pharmacol. 23(Suppl 2):S38–S41.
  10. DiPette DJ, Christenson W, Nickols MA, Nickols GA. 1992 Cardiovascular responsiveness to parathyroid hormone (PTH) and PTH-related protein in genetic hypertension. Endocrinology. 130:2045–2051.[Abstract]
  11. Massfelder T, Parekh N, Endlich K, Saussine C, Steinhausen M, Helwig JJ. 1996 Effect of intrarenally infused parathyroid hormone-related protein on renal blood flow and glomerular filtration rate in the anaesthetized rat. Br J Pharmacol. 118:1995–2000.[Medline]
  12. Everhart-Caye M, Inzucchi SE, Guinness Henry J, Mitnick MA, Stewart AF. 1996 Parathyroid hormone (PTH)-related protein-(1–36) is equipotent to PTH(1–34) in humans. J Clin Endocrinol Metab. 81:199–208.[Abstract]
  13. Philbrick WM, Wysolmerski JJ, Galbraith S, et al. 1996 Defining the roles of parathyroid hormone-related protein in normal physiology. Physiol Rev. 76:127–173.[Abstract/Free Full Text]
  14. Aellig WH. 1994 Clinical pharmacology, physiology and pathophysiology of superficial veins–1. Br J Clin Pharmacol. 38:181–196.[Medline]
  15. Aellig WH. 1994 Clinical pharmacology, physiology and pathophysiology of superficial veins–2. Br J Clin Pharmacol. 38:289–305.[Medline]
  16. McEwan JR, Benjamin N, Larkin S, Fuller RW, Dollery CT, MacIntyre I. 1988 Vasodilatation by calcitonin gene-related peptide and by substance P: a comparison of their effects on resistance and capacitance vessels of human forearms. Circulation. 77:1072–1080.[Abstract/Free Full Text]
  17. Blöchl-Daum B, Korn A, Wolzt M, Schmidt E, Eichler HG. 1991 In vivo studies on alpha-adrenergic receptor subtypes in human veins. Naunyn Schmiedebergs Arch Pharmacol. 344:302–307.[Medline]
  18. Schnurr E, Lahme W, Kuppers H. 1980 Measurement of renal clearance of inulin and PAH in the steady state without urine collection. Clin Nephrol. 13:26–29.[Medline]
  19. Prescott LF, Freestone S, McAuslane JA. 1993 The concentration-dependent disposition of intravenous p-aminohippurate in subjects with normal and impaired renal function. Br J Clin Pharmacol. 35:20–29.[Medline]
  20. Wolzt M, Schmetterer L, Ferber W, et al. 1997 Effect of nitric oxide synthase inhibition on renal hemodynamics in humans: reversal by L-arginine. Am J Physiol. 272:F178–F182.
  21. Weissler AM, Harris WS, Schoenfeld CD. 1968 Systolic time intervals in heart failure in man. Circulation. 37:149–159.[Abstract/Free Full Text]
  22. de Mey C, Belz GG, Nixdorf U, et al. 1992 Relative sensitivity of four noninvasive methods in assessing systolic cardiovascular effects of isoproterenol in healthy volunteers. Clin Pharmacol Ther. 52:609–619.[Medline]
  23. Wolzt M, Schmetterer L, Rheinberger A, et al. 1995 Comparison of non-invasive methods for the assessment of haemodynamic drug effects in healthy male and female volunteers: sex differences in cardiovascular responsiveness. Br J Clin Pharmacol. 39:347–359.[Medline]
  24. Waugh WH, Beall PT. 1974 Simplified measurement of p-aminohippurate and other arylamines in plasma and urine. Kidney Int. 5:429–436.[Medline]
  25. Fraher LJ, Klein K, Marier R, et al. 1995 Comparison of the pharmacokinetics of parenteral parathyroid hormone-(1–34) [PTH-(1–34)] and PTH-related peptide-(1–34) in healthy young humans. J Clin Endocrinol Metab. 80:60–64.[Abstract]
  26. Ogino K, Burkhoff D, Bilezikian JP. 1995 The hemodynamic basis for the cardiac effects of parathyroid hormone (PTH) and PTH-related protein. Endocrinology. 136:3024–3030.[Abstract]
  27. Endlich K, Massfelder T, Helwig JJ, Steinhausen M. 1995 Vascular effects of parathyroid hormone and parathyroid hormone-related protein in the split hydronephrotic rat kidney. J Physiol (Lond). 483:481–490.[Medline]
  28. Massfelder T, Stewart AF, Endlich K, Soifer N, Judes C, Helwig JJ. 1996 Parathyroid hormone-related protein detection and interaction with NO and cyclic AMP in the renovascular system. Kidney Int. 50:1591–1603.[Medline]
  29. Saussine C, Massfelder T, Parnin F, Judes C, Simeoni U, Helwig JJ. 1993 Renin stimulating properties of parathyroid hormone-related peptide in the isolated perfused rat kidney. Kidney Int. 44:764–773.[Medline]
  30. Fraher LJ, Hodsman AB, Jonas K, et al. 1992 A comparison of the in vivo biochemical responses to exogenous parathyroid hormone-(1–34) [PTH-(1–34)] and PTH-related peptide-(1–34) in man. J Clin Endocrinol Metab. 75:417–423.[Abstract]



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