Safety and effectiveness of daily teriparatide in a prospective observational study in patients with osteoporosis at high risk of fracture in Japan: final report

Figures & data

Table 1 Baseline demographics, disease characteristics, comorbidities, and previous or concomitant osteoporosis treatments of patients with osteoporosis at high risk of fracture in Japan

Characteristics	Patients (N=1,847)
Age
Mean (SD), years	75.4 (9.1)
Median (min, max), years	76 (31, 101)
30 to <50 years, n (%)	19 (1.0)
50 to <65 years, n (%)	210 (11.4)
65 to <75 years, n (%)	531 (28.7)
75 to <85 years, n (%)	839 (45.4)
≥85 years, n (%)	248 (13.4)
Height, mean (SD), cm	148.0 (7.8)
Weight, mean (SD), kg	47.3 (8.9)
Females, n (%)	1,711 (92.6)
Menopause status, n (%)
Premenopause	9 (0.5)
Postmenopause	1,554 (90.8)
Unknown	148 (8.6)
Age at menopause, mean (SD), yearsa	48.9 (4.8)
Current smoker, n (%)b	35 (1.9)
Alcohol consumption (>3 U/d), n (%)b	29 (1.6)
History of fracture, n (%)b	1,180 (63.9)
Past surgery for fracture, n (%)	243 (13.2)
History of proximal femoral fracture in patients’ parents, n (%)b	76 (4.1)
Vertebral fractures, n (%)	962 (52.1)
1	370 (20.0)
2	230 (12.5)
≥3	362 (19.6)
Nonvertebral fractures, n (%)	238 (12.9)
1	191 (10.3)
2	36 (1.9)
≥3	11 (0.6)
BMD, % of YAM, n (%)b
≥80%	133 (7.2)
70 to <80%	150 (8.1)
<70%	670 (36.3)
CKDb stage, n (%)
1	194 (10.5)
2	710 (38.4)
3	350 (18.9)
4	30 (1.6)
5	3 (0.2)

Notes:

a Information on age at menopause was available for 598/1,554 postmenopausal female patients.

b Information was not available on history of fracture for 224 patients; history of femoral fracture in patients’ parents for 872 patients; BMD for 894 patients; CKD for 560 patients; current smoking status for 410 patients; and alcohol consumption for 442 patients from the 1,847 patient cohort.

Abbreviations: BMD, bone mineral density; CKD, chronic kidney disease; min, minimum; max, maximum; n, number; SD, standard deviation; YAM, young adult mean.

Table 2 Adverse drug reactions in patients with osteoporosis at high risk of fracture following treatment with teriparatide in Japan

Adverse drug reaction	N=1,847 n (%)
Patients experiencing adverse drug reactions	140 (7.58)
Total adverse drug reactions reported	157
Most commonly reported reactionsa
Hyperuricemia	19 (1.03)
Nausea	16 (0.87)
Dizziness	10 (0.54)
Headache	9 (0.49)
Increased blood alkaline phosphate	7 (0.38)
Palpitations	6 (0.32)
Hypercalcemia	5 (0.27)
Rash	5 (0.27)
Decreased appetite	4 (0.22)
Renal impairmentb	4 (0.22)
Abdominal discomfort	3 (0.16)
Eczema	3 (0.16)
Pruritus	3 (0.16)
Urticaria	3 (0.16)
Feeling abnormalb	3 (0.16)
Patients experiencing serious adverse drug reactions	6 (0.32)
Total serious adverse drug reactions reported	7
Nausea	2 (0.11)
Constipation	1 (0.05)
Hypercalcemia	1 (0.05)
Toxic skin eruption	1 (0.05)
Calculus bladder	1 (0.05)
Renal impairment	1 (0.05)

Notes:

a Adverse drug reactions reported in >2 (0.1%) patients in the safety analysis.

b Adverse drug reactions that are not described in the usage notes for the study drug.

Abbreviation: n, number.

Figure 1 Kaplan–Meier curve of persistence with teriparatide treatment in patients with osteoporosis at high risk of fracture in Japan.

Figure 2 Percent change from baseline in biomarkers of bone turnover (median, Q1, Q3) and BMD (mean, 95% CI) after up to 24 months of teriparatide treatment and at LOCF in patients with osteoporosis at high risk of fracture in Japan.

Notes: Biomarkers for bone formation were PINP (A) and bone ALP (B) and for bone resorption were CTX-I (C) and TRACP5b (D). The mean (SD) baseline values were: PINP 51.49 (59.49) ng/mL; bone ALP 19.37 (17.45) IU/L; CTX-I 0.22 (0.16) ng/mL; and TRACP5b 451.50 (245.29) mU/dL. BMD was measured at the lumbar spine (E), femoral neck (F), and total hip (G). *P<0.05 for the increase from baseline at each time point.
Abbreviations: bone ALP, bone-specific alkaline phosphatase; BL, baseline; BMD, bone mineral density; CI, confidence interval; CTX-I, collagen type I cross-linked C telopeptide; LOCF, last observation carried forward; PINP, procollagen type I N-terminal propeptide; Q1, first quartile; Q3, third quartile; SD, standard deviation; TRACP5b, tartrate-resistant acid phosphatase 5b.

Figure 3 Kaplan–Meier estimate of vertebral (A) and nonvertebral (B) fractures in patients with osteoporosis at high risk of fracture during treatment with teriparatide in Japan.

Figure S1 LS mean (95% CI) change from baseline in back pain VAS score after 3, 12, 18, and 24 months of teriparatide treatment and at the last observation carried forward in patients with osteoporosis at high risk of fracture in Japan.

Note: *P<0.001 for the change from baseline at each time point.

Abbreviations: BL, baseline; CI, confidence interval; LOCF, last observation carried forward; LS, least squares; VAS, Visual Analog Scale.

Figure S2 Mean (95% CI) change from BL in SF-8 domains and SF-8 physical and mental component summary scores at 3, 12, 18, and 24 months of teriparatide treatment, and at the LOCF in patients with osteoporosis at high risk of fracture in Japan.

Notes: *P<0.001 for all SF-8 domains and summary scores at all time points. The mean (SD) BL scores were: (A) general health 44.7 (7.62); (B) physical functioning 39.9 (10.59); (C) role physical 38.6 (11.73); (D) bodily pain 41.6 (9.09); (E) vitality 45.1 (7.74); (F) social functioning 40.7 (11.09); (G) mental health 46.2 (8.21); (H) role emotional 42.3 (11.81); (I) physical component summary 38.4 (9.32); and (J) mental component summary 45.9 (9.17).

Abbreviations: BL, baseline; CI, confidence interval; LOCF, last observation carried forward; SD, standard deviation; SF-8, Short Form-8.

Table S1 Baseline comorbidities and previous or concomitant osteoporosis treatments of patients with osteoporosis at high risk of fracture in Japan

Characteristic	N=1,847 n (%)
Comorbidities	893 (48.3)
Most frequently occurring comorbidities
Hypertension	306 (16.6)
Rheumatoid arthritis	151 (8.2)
Hyperlipidemia	140 (7.6)
Osteoarthritis	105 (5.7)
Constipation	97 (5.3)
Gastroesophageal reflux disease	94 (5.1)
Insomnia	86 (4.7)
Lumbar spinal canal stenosis	83 (4.5)
Type 2 diabetes mellitus	77 (4.2)
Gastritis	66 (3.6)
Renal impairmenta	404 (21.9)
Hepatic impairmentb	217 (11.7)
Secondary osteoporosisc	148 (8.0)
Glucocorticoid-induced osteoporosisc	148 (8.0)
Past medical history	598 (32.4)
Most frequently reported medical history
Vertebral compression fracture	58 (3.1)
Uterine leiomyoma	51 (2.8)
Appendicitis	41 (2.2)
Cerebral infarction	35 (1.9)
Femoral neck fracture	28 (1.5)
Gastric ulcer	27 (1.5)
Hypertension	25 (1.4)
Osteoarthritis	22 (1.2)
Lumbar spinal canal stenosis	21 (1.1)
Cataract	21 (1.1)
History of drug therapy for osteoporosis	1,101 (59.6)
Most common previous drug therapy for osteoporosis (used by ≥5 patients)
Alendronate (oral)	493 (26.7)
Alfacalcidol (oral)	311 (16.8)
Risedronate (oral)	266 (14.4)
Raloxifene (oral)	190 (10.3)
Elcatonin (intramuscular)	113 (6.1)
Minodronic acid (oral)	89 (4.8)
Menatetrenone (oral)	58 (3.1)
Calcitriol (oral)	52 (2.8)
l-Aspartic acid (oral)	34 (1.8)
Eldecalcitol (oral)	18 (1.0)
Bazedoxifene (oral)	15 (0.8)
Concomitant drug therapy for osteoporosis	406 (22.0)
Most common concomitant drug therapy for osteoporosis (used by ≥5 patients)
l-aspartic acid (oral)	176 (9.5)
Alfacalcidol (oral)	145 (7.9)
Menatetrenone (oral)	101 (5.5)
Eldecalcitol (oral)	39 (2.1)
Elcatonin (intramuscular)	34 (1.8)
Raloxifene (oral)	31 (1.7)
Risedronate (oral)	28 (1.5)
Alendronate (oral)	13 (0.7)
Minodronic acid (oral)	10 (0.5)
Bazedoxifene (oral)	7 (0.4)

Notes:

a Patients with renal impairment or chronic kidney disease stages 3 to 5 are defined as having renal impairment.

b Patients with liver impairment or abnormal laboratory data regarding liver function (aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl transpeptidase exceeded standard level) are defined as having hepatic impairment.

c Information was not available on secondary osteoporosis for 328 patients or on glucocorticoid-induced osteoporosis for 337 patients.

Abbreviation: n, number.