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Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2006-2439
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The Journal of Clinical Endocrinology & Metabolism Vol. 92, No. 9 3535-3541
Copyright © 2007 by The Endocrine Society

Occurrence of Hypercalciuria in Patients with Osteoporosis Treated with Teriparatide

Paul D. Miller, John P. Bilezikian, Manuel Diaz-Curiel, Peiqi Chen, Fernando Marin, John H. Krege, Mayme Wong and Robert Marcus

Colorado Center for Bone Research (P.D.M.), Lakewood, Colorado 80227; Columbia University College of Physicians and Surgeons (J.P.B.), New York, New York 10032; Fundación Jiménez Díaz (M.D.-C.), 2-28040, Madrid, Spain; and Lilly Research Laboratories (P.C., F.M., J.H.K., M.W., R.M.), Eli Lilly and Co., Indianapolis, Indiana 46285

Address all correspondence and requests for reprints to: Paul D. Miller, M.D., F.A.C.P., Colorado Center for Bone Research, 3190 South Wadsworth, Suite 250, Lakewood, Colorado 80227. E-mail: MillerCCBR{at}aol.com.


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Discussion
 References
 
Context: Teriparatide (TPTD) [recombinant human PTH(1–34)] given sc once daily transiently increases serum calcium concentrations at 4–6 h after dosing, but its effects on urinary calcium excretion are less well studied.

Objective: Our objective was to evaluate urinary calcium excretion, a prespecified safety endpoint, for up to 12 months of TPTD treatment.

Design: This study included two prospective, randomized, double-blind placebo-controlled clinical trials.

Participants: A total of 2074 participants with osteoporosis or low bone mass (study 1, 1637 postmenopausal women; study 2, 437 men) were included.

Interventions: Participants were given calcium (1000 mg/d) and vitamin D (400–1200 IU/d) supplements, and were randomized to placebo, TPTD 20 µg/d, or TPTD 40 µg/d.

Main Outcome Measures: Urinary calcium excretion was measured in 24-h collections at baseline, 1, 6, and 12 months.

Results: In each study, baseline urinary calcium excretion was similar among groups. All groups had significantly increased urinary calcium excretion, compared with baseline, at most post-baseline time points. Post-baseline urinary calcium excretion was increased in the TPTD 20 µg/d group by up to 32 mg/d compared with placebo at the same time point (P < 0.05) in study 1. A total of seven participants (0.3%), of which three and four were in the placebo and TPTD groups, respectively, discontinued study drug due to repeated hypercalciuria (>300 mg/d).

Conclusion: Urinary calcium excretion was increased with TPTD treatment for up to 12 months, compared with placebo and baseline values, but the magnitude of these changes is unlikely to be clinically relevant or warrant urinary calcium monitoring for most patients.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Discussion
 References
 
PTH MAINTAINS CALCIUM homeostasis by stimulating calcium and phosphate release from the skeleton, and by promoting calcium reabsorption and inhibiting phosphate reabsorption in the kidney (1, 2). PTH also enhances the synthesis of 1,25-dihydroxyvitamin D, which in turn increases calcium and phosphate absorption from the intestine. The net results of PTH-related actions are increased serum calcium and decreased serum phosphate concentrations (2). Prolonged elevation of PTH concentrations, such as in primary hyperparathyroidism, lead to greater bone resorption and decreased bone mineral density (BMD), and is associated with hypercalcemia, hypercalciuria, and nephrolithiasis (3). In contrast, a once-daily injection of PTH gives a transient increase in PTH that produces bone anabolic effects and increases BMD (1), although effects on urinary calcium excretion, in relation to serum calcium concentrations, are less well characterized.

Teriparatide (TPTD) [recombinant human PTH(1–34); Eli Lilly and Co., Indianapolis, IN], given as a single 20-µg/d sc injection, is approved for treatment of osteoporosis in postmenopausal women (4, 5) and, in some countries, in men at high risk for fracture (5). In clinical trials, TPTD at either 20 µg/d (TPTD20) or 40 µg/d (TPTD40) has significantly decreased fracture risk (6), and increased BMD (6, 7) and biochemical markers of bone formation and resorption (7, 8, 9). After administration of TPTD20, serum calcium concentrations increase transiently beginning 2 h after injection, peak between 4 and 6 h after dosing, and return to baseline values at 16–24 h after dosing (1, 6).

The effects of TPTD on urinary calcium excretion, whether these effects are sustained with therapy and reflect changes in serum calcium, are not known. Some clinical trials have noted increased urinary calcium excretion with TPTD therapy, but no detailed analyses on the occurrence of hypercalciuria with TPTD have been published. The primary objective of this analysis is to examine further urinary calcium excretion and the incidence of hypercalciuria [>300 mg/d (7.5 mmol/d)] over 12 months in 2074 participants treated with TPTD from two placebo-controlled clinical trials, in which urinary calcium excretion data were collected as a prespecified safety endpoint. In addition, cases of urolithiasis obtained from safety analyses of these trials are reported.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Discussion
 References
 
Study designs and participants

Urinary calcium excretion was measured in five multicenter, prospective, parallel, randomized, double-blind clinical trials with TPTD. The present analysis included data from the two placebo-controlled clinical studies of participants with osteoporosis or low bone mass, confirmed by BMD measurements and/or the presence of fractures at baseline. The effects of placebo, TPTD20, and TPTD40 were compared in 1637 postmenopausal women in study 1 (6) and in 437 men in study 2 (7). Both studies were originally planned to last for 36 and 24 months, respectively, but were terminated early, resulting in shorter treatment duration, after a long-term carcinogenicity study of rats treated with TPTD showed osteosarcomas (10). Prespecified safety endpoints in both studies included clinical adverse events, serum calcium concentrations, and 24-h urinary calcium excretion and creatinine clearance. All participants received daily oral supplements of elemental calcium 1000 mg, as the carbonate salt, and vitamin D 400-1200 IU, beginning 1 month before randomization and for the duration of the studies. Baseline 24-h urinary calcium excretion was measured at randomization. Patient compliance was assessed by direct questioning and pill count.

Participants in both studies were ambulatory and free of chronic, disabling conditions other than osteoporosis or low bone mass. Exclusion criteria included diseases that affect bone or calcium metabolism, nephrolithiasis, or urolithiasis within the preceding 2 (study 2) or 5 yr (study 1), impaired hepatic or renal function, with the latter defined as serum creatinine concentration exceeding 2 mg/dl (177 µmol/liter). Persons who had taken drugs that alter bone metabolism, such as androgens, bisphosphonates, calcitonin, glucocorticoids, estrogen agonists or antagonists, and fluorides, within the previous 2–24 months (depending on the drug) were also excluded from these studies. In study 2, hypogonadal men whose doses of androgens or testosterone replacement therapy were stable for at least 6 months before randomization were eligible for the study and continued such therapy during the study. However, men with GH deficiency from any cause, or who had suspected carcinoma or history of carcinoma (except for skin cancer) within the past 5 yr, were also excluded from study 2. Ethical review committees at each study center approved the respective study protocols. All participants gave written informed consent before study enrollment. All study methods and procedures were conducted in accordance with the Declaration of Helsinki.

Urinary calcium and creatinine measurements

In both studies, calcium and creatinine excretion were measured in 24-h urine collections at baseline, 1, 6, and 12 months, and the final study visit. Due to the variability in both urinary calcium excretion and collection volume, all evaluations of 24-h urine collection were based on total urinary calcium, total urinary creatinine excretion (to assess the adequacy of the collection), and urinary calcium to creatinine ratio, to help correct for the variability in the completeness of the collection (11). Any participant who may have had over-collection had the test repeated. The date of the repeated laboratory test was at the discretion of the investigator. Subsequent evaluations consisted of assessing urinary calcium excretion alone, with the upper limit of the normal range defined as 300 mg/d (7.5 mmol/d) (12, 13). These limits are comparable to the 95th percentile of urinary calcium excretion (286 mg/d or 4.52 mg/kg·d) in estrogen-deprived, normal, middle-aged women with a dietary calcium intake of 500-1000 mg/d (14). In each study, additional analyses calculated the proportion of participants with hypercalciuria defined as more than 4 mg/kg·d when urinary calcium excretion is normalized by baseline body weight (12, 13), and with hypercalciuria defined as more than 350 mg/d.

If urinary calcium excretion was still elevated upon repeated testing, then the calcium supplement dose was reduced or discontinued upon the investigator’s discretion. At the investigator’s discretion, the dose of the injectable study material was halved, either concomitantly or sequentially, with reduction in the calcium supplement dose. The injectable study material was permanently discontinued if urinary calcium excretion remained elevated after the dose of the injectable study material was reduced. The urinary calcium excretion test was repeated until the values returned to the normal range. In both studies this dose reduction algorithm was also used if participants had increased serum calcium at 4–6 h after the dose, or if participants reported symptoms such as nausea or headache. The reason for dose reduction was not recorded, so the number of participants who had dose reductions due to elevated urinary calcium may be overestimated. Any permanent change in the calcium supplement dose or injectable study material was recorded.

Adverse events

At each clinic visit, participants were questioned about the occurrence and severity of adverse events. All adverse events that were new or worsened after randomization were considered to be treatment-emergent adverse events, regardless of relationship to study drug. All participants who were randomized were included in the analysis of treatment-emergent adverse events related to kidney or urinary tract calculi or related disorders.

Statistical analysis methods

Because the data for urinary calcium excretion and urinary calcium to creatinine ratios were not normally distributed, rank transformation (15) was applied before statistical analyses were performed. The placebo and TPTD groups were compared using ANOVA based on ranked data. Effects in the ANOVA model included treatment and investigator. The summary statistics for urinary calcium excretion and urinary calcium to creatinine ratios were expressed as median and interquartile range (25th, 75th) for each treatment group. T changes from baseline to postbaseline at different time points in urinary calcium excretion and urinary calcium/creatinine were assessed using the paired t test. The {chi}2 tests were used to compare the proportions of participants with hypercalciuria among groups at any time point. McNemar’s test (16) was used to determine any significant change in the proportions of participants with hypercalciuria within each treatment group from baseline to postbaseline. Fisher’s exact tests were used to assess the association between hypercalcemia and hypercalciuria in patients within each treatment group at individual time points. Statistical inferences were made based on a two-sided significance level of 0.05.


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Discussion
 References
 
Baseline characteristics

Table 1Go summarizes the overall baseline characteristics in the pooled treatment groups for each trial. There were no significant differences in any of the baseline characteristics among treatment groups within each trial, as described in the primary publications (6, 7). In both studies, 99% of participants were Caucasian.


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  		TABLE 1. Overall baseline characteristics of participants in two placebo-controlled clinical studies with TPTD

 
Median 24-h urinary calcium excretion

In study 1, both TPTD groups had significantly higher urinary calcium excretion at 1 and 6 months, compared with baseline (Table 2Go). Urinary calcium excretion was greater in the TPTD20 group compared with placebo by 20 mg/d at 1 month (P = 0.005), 31 mg/d at 6 months (P < 0.001), and 12 mg/d at 12 months (P = 0.030). At 6 months, urinary calcium excretion in the TPTD40 group was 16 mg/d greater than that in the placebo group (P = 0.003). In study 2, urinary calcium excretion was significantly increased compared with baseline at 1 and 6 months in the placebo and both TPTD groups (Table 2Go). Compared with baseline, urinary calcium excretion was increased at 12 months by a median of 32 mg/d in the placebo group (P = 0.010) and 20 mg/d in the TPTD20 group (P = 0.003). There were no significant differences in the TPTD groups when compared with placebo at 1, 6, or 12 months in study 2.


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  		TABLE 2. Urinary calcium excretion (mg/24 h) in participants with ≥1 post-baseline urine measurement

 
Because urinary calcium excretion values are influenced by differences in body weight, the aforementioned calculations were repeated with adjustments for baseline body weight and urinary creatinine excretion. Baseline urinary calcium excretion in the placebo group was 2.5 mg/kg·d (1.7, 3.4) [median (interquartile range)] in study 1 and 2.7 mg/kg·d (1.8, 3.7) in study 2. There were no baseline differences among groups in studies 1 and 2. When adjusted for body weight, the increases in urinary calcium excretion followed similar trends (data not shown) as in Table 2Go. In the placebo groups of studies 1 and 2, urinary calcium excretion did not significantly increase from baseline to 12 months. In study 1, urinary calcium excretion in the TPTD20 group was significantly higher compared with placebo by 0.2 mg/kg·d at 1 month and 0.4 mg/kg·d at 6 months. At 1 month in study 2, urinary calcium excretion in the TPTD20 and TPTD40 groups was significantly increased compared with baseline, but the increases in the TPTD groups were not significantly different when compared with placebo (data not shown).

In both studies baseline urinary calcium to creatinine ratios were similar among groups. All treatment groups had significant increases in the urinary calcium to creatinine ratios at 1, 6, and 12 months when compared with baseline (data not shown). In study 1, the urinary calcium to creatinine ratios were significantly greater compared with placebo in the TPTD20 group at 1, 6, and 12 months, and in the TPTD40 group at 1 and 6 months (all P < 0.05). In study 2, the urinary calcium to creatinine ratios were not significantly different in the TPTD groups compared with placebo at 1, 6, and 12 months.

Proportions of participants with hypercalciuria

In both studies the proportions of participants with hypercalciuria (>300 mg/d) were higher in the TPTD groups at 1 and/or 6 months compared with baseline (Fig. 1Go; P < 0.05), but the TPTD groups were not statistically different, compared with placebo, at 1, 6, and 12 months. When urinary calcium excretion normalized by baseline body weight (Fig. 2Go), more women in the TPTD groups, compared with placebo (P < 0.05), had hypercalciuria (>4 mg/kg·d) at 6 months.


Figure 1
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  		FIG. 1. Proportions of participants (%) with hypercalciuria based on urinary calcium excretion [>300 mg/d (>7.5 mmol/d)]. A, Study 1 contained 1604 postmenopausal women with osteoporosis. B, Study 2 contained 418 men with low bone mass. a, P < 0.05 compared with the same treatment group at baseline.

 

Figure 2
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  		FIG. 2. Proportions of participants (%) with hypercalciuria based on urinary calcium excretion with adjustment for baseline body weight [>4 mg/kg·d (0.1 mmol/kg·d)]. A, Study 1 contained 1604 postmenopausal women with osteoporosis. B, Study 2 contained 418 men with low bone mass. a, P < 0.05 compared with the same treatment group at baseline. b, P < 0.05 compared with placebo at the same time point.

 
Further analyses examined the proportions of participants with hypercalciuria defined as urinary calcium excretion more than 350 mg/d. In study 1, between 4.8 and 11% of women in the TPTD20 group had hypercalciuria at 1, 6, and 12 months, compared with 3.2% at baseline (P < 0.05). However, the incidence of hypercalciuria was not statistically different between the placebo and TPTD20 groups at 1, 6, and 12 months (data not shown). In study 2, more men treated with TPTD20 (18.2%) had hypercalciuria at 1 month compared with baseline (9.9%; P < 0.05), but the incidence of hypercalciuria at 1, 6, and 12 months was not statistically different between the placebo and TPTD20 groups (data not shown).

The association between hypercalciuria at baseline and on one or more occasions after baseline was examined in 1578 women with paired baseline and postbaseline urinary calcium measurements from study 1. Regardless of treatment group, baseline urinary calcium excretion was higher in women who developed postbaseline hypercalciuria [median (interquartile range); 228.0 (176.0, 269.7)], than in those who did not [140.0 (96.0, 192.0); P = 0.001]. In the 108 women with baseline hypercalciuria, the proportions of women with one or more episode of postbaseline hypercalciuria were not statistically different among groups (placebo, 64.3%; TPTD20, 62.9%; and TPTD40, 64.3%). Of the 1470 women with normal baseline urinary calcium excretion, the proportions of women who had one or more episodes of postbaseline hypercalciuria were not statistically different among groups (placebo, 24.1%; TPTD20, 20.3%; and TPTD40, 17.4%). A greater proportion of women with baseline hypercalciuria, compared with women with normal urinary calcium excretion at baseline, continued to have hypercalciuria at 1, 6, or 12 months (P = 0.001). In the 69 women with baseline hypercalciuria who continued to have postbaseline hypercalciuria, the change in urinary calcium excretion was 0.1 mg/d (–1.3, 2.2) [median (interquartile range)].

Occurrence of hypercalciuria and hypercalcemia

In the study 1 cohort, baseline serum calcium concentrations were similar in women with or without postbaseline hypercalciuria (P = 0.37). In all treatment groups, less than 1% of participants had concurrent hypercalciuria and hypercalcemia, whereas the majority (>80%) had normal urine and serum calcium concentrations. In the TPTD20 group at 12 months, three women (0.6%) had both hypercalciuria and hypercalcemia, 49 (10.4%) had hypercalciuria with normal serum calcium, five (1.1%) had normal urinary calcium excretion and hypercalcemia, and 419 (87.9%) had normal urine calcium excretion and normal serum calcium concentrations. Although this association reached statistical significance (P = 0.047), there were no other statistically significant associations in the TPTD20 group at 1 or 6 months, or in the placebo or TPTD40 groups at 1, 6, or 12 months. For the relationship between urinary calcium and serum calcium values, the correlation coefficients ranged between 0.12 and 0.32 in all groups at 1, 6, and 12 months (P < 0.01), except for TPTD40 at 12 months (r = 0.06; P = 0.23).

Dose reductions of calcium or study drug

In study 1, there were no statistically significant differences among groups in the proportions of women with hypercalciuria on more than two consecutive occasions, or who had dose reductions for calcium or study drug. The proportions of women who had hypercalciuria on more than two consecutive occasions ranged between 2.6 and 4.9%. Calcium doses were reduced in 5.0, 8.3, and 9.1% of women in the placebo, TPTD20, and TPTD40 groups, respectively. Doses of study drug were reduced in 1.3, 3.0, and 3.8% of women in the placebo, TPTD20, and TPTD40 groups, respectively. Three women (0.6%) in the placebo group, one (0.2%) in the TPTD20 group, and two (0.4%) in the TPTD40 group were discontinued from study drug due to hypercalciuria.

In study 2, no men in the placebo group and 1.4% of men in the TPTD groups had hypercalciuria on more than two consecutive occasions. One man in each of the placebo and TPTD40 groups, and two men in the TPTD20 group had adjustments in calcium dose, whereas none in any group had a study drug dose reduction. One man (0.7%) in the TPTD20 group was discontinued from study drug due to hypercalciuria.

Adverse events related to the kidney or urinary tract

In study 1, two women in each of the placebo and TPTD20 groups had a kidney calculus, and one woman in each TPTD group had urinary tract calcifications. Kidney pain, a symptom compatible with urolithiasis, was reported by three women in the TPTD20 group and one in the TPTD40 group. In total, two women in the placebo group, six in the TPTD20 group, and two in the TPTD40 group had possible urolithiasis. In addition, six women in the placebo group and four women in each of the TPTD groups reported hematuria. In study 2, a total of five men had possible urolithiasis. One man in the placebo group, two in the TPTD20 group, and one in the TPTD40 group had a kidney calculus. One man in the TPTD40 group reported kidney pain. Further evaluations were not performed to confirm these cases of possible urolithiasis in either study.


   Discussion
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
References
 
These results indicate no consistent trends for elevated urinary calcium excretion related to TPTD treatment. In study 1, the TPTD20 group had increases in urinary calcium excretion, which were small in magnitude but statistically significant at 1, 6, and 12 months compared with baseline and placebo, when calculated alone or normalized to either body weight or creatinine excretion. In study 2, urinary calcium excretion was not significantly different between the placebo and TPTD groups at baseline, 1, 6, and 12 months. In studies 1 and 2, the proportion of participants in the TPTD groups with hypercalciuria (>300 mg/d) was significantly greater compared with baseline but was not statistically different between the placebo and TPTD groups at 1, 6, and 12 months. Regardless of the treatment group, those participants who had hypercalciuria at baseline were more likely to experience hypercalciuria at 1, 6, or 12 months. Many cases of postbaseline hypercalciuria were not sustained because only about 3% of participants had more than two consecutive elevated urinary calcium measurements in these studies.

Although the present analyses focused on the two largest, placebo-controlled trials, urinary calcium excretion was also measured in three other trials in which TPTD was combined or compared with antiresorptive agents. Urinary calcium excretion was not statistically different in women given TPTD20 plus raloxifene 60 mg/d compared with those given TPTD20 plus placebo (17). In women given TPTD40, urinary calcium excretion at 1 month was increased by 38 mg/d from baseline (P = 0.001 compared with baseline, and with alendronate 10 mg/d), with no differences between the TPTD40 and alendronate groups after 1 month (18). In the TPTD40 and alendronate groups, 30 and 22% of women, respectively, had at least one elevated urinary calcium value. In women treated with hormone therapy (conjugated equine estrogens, 0.625 mg/d and medroxyprogesterone, 2.5 mg/d), no significant differences in urinary calcium excretion were seen (Eli Lilly and Co., data on file) compared with women given combined TPTD40 and hormone therapy (19), although a greater proportion of women in the combined therapy group (9.9%) had hypercalciuria at 1 month than in the hormone therapy group (1.7%) (P = 0.007; Eli Lilly and Co., data on file).

Increases in serum calcium concentrations have been reported in studies 1 and 2. In study 1, hypercalcemia, defined as serum calcium more than 10.6 mg/dl (2.65 mmol/liter) at 4-h after a dose, was seen on one or more occasions in 2, 11, and 28 of women treated with placebo, TPTD20, and TPTD40, respectively (6). One participant in each of the placebo and TPTD20 groups had predose (>16 h after injection) hypercalcemia in study 1 (20). Women who did not have hypercalcemia within the first 6 months of treatment seldom had hypercalcemia at later time points (6). In study 2, 0, 6.2, and 16.8% of men in the placebo, TPTD20, and TPTD40 groups, respectively, had hypercalcemia at 4–6 h after a dose (7), but none had hypercalcemia at 16–24 h after a dose (Eli Lilly and Co., data on file). The correlations between the occurrence of hypercalcemia and hypercalciuria in studies 1 and 2 reached statistical significance due to the large number of patients but were not likely to be clinically significant because the magnitude of the coefficients was small.

Product labeling for TPTD20 does not specify monitoring serum calcium, although urinary calcium excretion measurement may be considered for patients suspected of having active urolithiasis or preexisting hypercalciuria (4, 5). However, some authors have suggested that patients have serum calcium, renal function, and creatinine clearance assessments performed before initiating TPTD therapy (21), and serum calcium measured 16 h postinjection after 1 month starting TPTD therapy (1).

Participants included in these studies had normal renal function before study entry, and were given adequate calcium and vitamin D supplementation, so these findings might only apply to patients with similar characteristics. Dose reductions for calcium or study drug may have affected the overall urinary calcium excretion results. Possibly due to the exclusion of patients with a history of recent nephrolithiasis or urolithiasis from these trials, few adverse events related to the urinary system were observed, and adverse events were based upon participant self-report and were not confirmed by further evaluation. Finally, these analyses included urinary calcium assessments for only the first 12 months of the studies, and subsequent urinary calcium excretion data were not available.

In summary, small increases from baseline in urinary calcium excretion were observed during 12 months of therapy with TPTD20 in study 1. TPTD40 did not consistently increase urinary calcium excretion. Neither dose of TPTD meaningfully increased the incidence of hypercalciuria compared with placebo. During adverse event monitoring, patients treated with TPTD did not have an excess of urolithiasis compared with placebo. Less than 1% of participants overall in both studies required dose adjustments for calcium or study drug due to hypercalciuria. The prudent physician might consider urinary calcium monitoring for some particular patients, such as those with a history of urolithiasis. These results suggest that urinary calcium monitoring is not necessary for the majority of patients taking TPTD.


   Acknowledgments
 
We acknowledge Gregory A. Gaich, M.D., of Lilly Research Laboratories, for study protocol design.


   Footnotes
 
Eli Lilly and Co. provided funding for the clinical studies described in this paper.

Disclosure Summary: P.D.M. has consulted for Proctor & Gamble, Sanofi/Aventis, Merck, Lilly, Amgen, NPS, Novartis, Roche, and GlaxoSmithKline, and has received grant support from Proctor & Gamble, Sanofi/Aventis, Roche, Merck, Lilly, Amgen, and Novartis. J.P.B. is a consultant for Amgen, Lilly, Merck, Alliance for Better Bone Health, NPS, and Radius Pharmaceuticals, and has received lecture fees from Lilly, Merck, and Alliance for Better Bone Health. M.D.-C. has received lecture fees from Eli Lilly and Co. P.C., F.M., J.H.K., M.W., and R.M. are employed by Eli Lilly and Co., and own stock in Eli Lilly and Co.

First Published Online July 3, 2007

Abbreviations: BMD, Bone mineral density; TPTD, teriparatide; TPTD20, TPTD 20 µg/d; TPTD40, TPTD 40 µg/d.

Received November 7, 2006.

Accepted June 22, 2007.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
 References
 

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