Safety of daily teriparatide treatment: a post hoc analysis of a Phase III study to investigate the possible association of teriparatide treatment with calcium homeostasis in patients with serum procollagen type I N-terminal propeptide elevation

Figures & data

Table 1 Demographics and baseline characteristics

	Placebo-teriparatide (N=67)	Teriparatide (N=136)
Age, years (SD)	70.4 (5.4)	69.2 (6.3)
Female, n (%)	62 (92.5)	127 (93.4)
Years since natural menopause (SD)a	20.5 (6.1)	19.7 (7.1)
No previous vertebral fracture, n (%)	38 (56.7)	82 (60.3)
BMI, kg/m^2 (SD)	22.2 (3.3)	21.6 (3.0)
BMD (L2–L4), g/cm^2 (SD)	0.638 (0.079)	0.639 (0.069)
Markers of bone turnover PINP, μg/L (SD)	55.6 (21.9)	55.7 (21.0)

Notes:

a Female subjects with natural menopause: 56 (placebo-teriparatide group); 119 (teriparatide group). Data are mean (SD) or n (%).

Abbreviations: BMD, bone mineral density; BMI, body mass index; PINP, procollagen type I N-terminal propeptide; SD, standard deviation; L, lumber spine.

Figure 1 Change in median serum procollagen type I N-terminal propeptide (PINP) from baseline to specific time points.

Notes: During the open-label phase from 12 to 24 months, all subjects received teriparatide 20 μg/day. Values are medians and error bars indicate the interquartile ranges (Q1–Q3). The dashed line denotes the placebo component of the study. The number of subjects at each time point is indicated below the x-axis.

Figure 2 Comparison of distribution of serum procollagen type I N-terminal propeptide (PINP) concentration at baseline to that at 1, 3, 6, and 12 months (A, B, C, and D, respectively) in the placebo (open markers) and teriparatide (shaded markers) groups.

Figure 3 Kaplan–Meier plot of time-to-onset of nausea (A), headache (B), leg cramp (C), and dizziness (D) in the placebo-teriparatide and teriparatide groups.

Note: The number of subjects at risk is indicated below the x-axis of each plot.

Figure 4 Median serum calcium concentration over time in the teriparatide (A) and placebo-teriparatide (B) groups.

Notes: L: subjects with serum procollagen type I N-terminal propeptide (PINP) levels ≤200 μg/L during the study period (n=117 and n=58 in the teriparatide and placebo-teriparatide groups, respectively). H: subjects with serum PINP levels >200 μg/L at any time point during the study period (n=19 and n=9 in the teriparatide and placebo-teriparatide groups, respectively). ^aAll measurements were corrected by albumin. ^bTime after starting teriparatide administration. The gray shaded component of the plot in (B) denotes the placebo component of the study. The horizontal line in the middle of each box represents the median, and the upper and lower edges of each box represent the interquartile range. The whiskers denote the largest and smallest values, and the open circles denote the outlying values.

Table 2 Adverse events related to abnormal bone metabolism, metastatic bone tumors, or other metabolic bone diseases

Time of onset after first dose, weeks	Adverse event		Serum PINP, μg/L		Serum calcium, mg/dL
	Reported term	MedDRA term	At baseline	At nearest visit (week)	At baseline		At nearest visit (week)
					Total	Corrected	Total	Corrected
36	Hypercalcemia	Hypercalcemia	32	120 (24) 96 (52)	9.1	8.7	12.3 (36)	12.0 (36)
88a	Hypercalcemia	Hypercalcemia	38	190 (76) 301 (104)	9.0	8.6	10.3 (88)	10.0 (88)
4	Periarthritis calcarea	Periarthritis calcarea	62	148 (4)	8.8	8.4	9.1 (4)	8.9 (4)
16	Polyarticular pseudogout	Chondrocalcinosis pyrophosphate	28	73 (12)	9.5	9.2	9.1 (12)	8.9 (12)
83	Pseudogout of right kneeb	Chondrocalcinosis pyrophosphate	65	76 (76)	9.3	9.1	9.4 (76)	9.3 (76)
86	Pseudogout of bilateral anklesb	Chondrocalcinosis pyrophosphate	65	76 (76)	9.3	9.1	9.4 (76)	9.3 (76)

Notes:

a Placebo was administered during the double-blind period.

b Pseudogout of the right knee and bilateral pseudogout of the ankles occurred in the same patient.

Abbreviations: MedDRA, Medical Dictionary for Regulatory Activities; PINP, procollagen type I N-terminal propeptide.