Effects of loratadine, a histamine H₁ receptor antagonist, on the skeletal system of young male rats

Figures & data

Table 1 Effects of loratadine (0.5–50 mg/kg p.o.) on the body mass gain, serum levels of total calcium, inorganic phosphorus, and bone turnover markers in young male rats

Parameter/group	C	L0.5	L5	L50
Initial body mass (g)	150.0 (135.0–168.0)	155.5 (140.0–174.0)	154.0 (140.0–179.0)	159.0 (152.0–182.0)
Body mass gain after four weeks (g)	122.0 (110.0–143.0)	124.5 (109.0–131.0)	118.0 (108.0–141.0)	116.0 (87.0–119.0)
Total calcium (mg/100 mL)	10.18 (9.67–11.15)	10.45 (9.36–11.15)	10.61 (9.91–11.39)	10.76 (9.91–11.70)
Inorganic phosphorus (mg/100 mL)	8.16 (7.39–10.42)	8.69 (7.36–9.71)	8.33 (6.83–9.37)	8.89 (7.49–9.78)
Osteocalcin (ng/mL)	327.4 (279.7–366.0)	329.8 (251.2–366.6)	301.2 (272.9–369.3)	292.6 (218.3–373.2)
CTX-I (ng/mL)	44.0 (37.7–63.3)	48.4 (40.4–57.3)	50.7 (40.2–73.5)	50.8 (40.3–63.3)

Notes: Results are presented as median (min–max); n=8–10. Loratadine at doses of 0.5 mg/kg, 5 mg/kg, or 50 mg/kg was administered orally, once daily for 4 weeks. The final measurements of the body mass were made before the last loratadine or vehicle administration. Kruskal–Wallis test followed by Mann–Whitney U test were used for statistical evaluation of loratadine effect in comparison with the control rats.

Abbreviations: C, control rats; CTX-I, C-terminal type I collagen fragments; L0.5, rats treated with loratadine at a dose of 0.5 mg/kg p.o.; L5, rats treated with loratadine at a dose of 5 mg/kg p.o.; L50, rats treated with loratadine at a dose of 50 mg/kg p.o.

Table 2 Effects of loratadine (0.5–50 mg/kg p.o.) on the length, mass, composition, and mineralization of the femur in young male rats

Parameter/Group	C	L0.5	L5	L50
Bone length (mm)	33.84 (33.02–34.92)	33.81 (32.81–34.70)	33.30 (29.72–34.33)	33.26 (32.30–33.67)**
Bone mass (g)	0.678 (0.622–0.718)	0.692 (0.635–0.739)	0.677 (0.593–0.722)	0.688 (0.580–0.729)
Bone mineral mass (g)	0.258 (0.244–0.276)	0.257 (0.245–0.289)	0.249 (0.211–0.273)	0.259 (0.206–0.286)
Mass of bone mineral /bone mass ratio	0.387 (0.359–0.402)	0.379 (0.361–0.400)	0.368 (0.355–0.396)	0.377 (0.355–0.414)
Mass of bone water /bone mass ratio	0.373 (0.341–0.407)	0.378 (0.355–0.396)	0.385 (0.362–0.399)	0.381 (0.333–0.404)
Mass of bone organic substances/bone mass ratio	0.241 (0.234–0.257)	0.244 (0.240–0.254)	0.246 (0.236–0.253)	0.241 (0.239–0.253)
Calcium content (g/g of bone mineral)	0.379 (0.352–0.391)	0.377 (0.358–0.404)	0.375 (0.352–0.387)	0.382 (0.358–0.404)
Phosphorus content (g/g of bone mineral)	0.163 (0.156–0.176)	0.160 (0.141–0.180)	0.161 (0.157–0.182)	0.162 (0.154–0.184)
Molar Ca/P ratio	1.79 (1.59–1.91)	1.86 (1.60–2.04)	1.80 (1.60–1.88)	1.82 (1.61–1.97)

Notes: Results are presented as median (min–max); n=8–10. Loratadine at doses of 0.5 mg/kg, 5 mg/kg, or 50 mg/kg was administered orally, once daily for 4 weeks. Kruskal–Wallis test followed by Mann–Whitney U test were used for statistical evaluation of loratadine effect in comparison with the control rats. ** P<0.01 in comparison with the control rats.

Abbreviations: C, control rats; Ca, calcium; L0.5, rats treated with loratadine at a dose of 0.5 mg/kg p.o.; L5, rats treated with loratadine at a dose of 5 mg/kg p.o.; L50, rats treated with loratadine at a dose of 50 mg/kg p.o.; P, phosphorus.

Figure 1 Effects of loratadine (0.5–50 mg/kg p.o.) on the composition and mineralization of the L-4 vertebra in young male rats. Results are presented as median (line), interquartile range (box), and minimum and maximum values (whiskers); n=8–10. Loratadine at doses of 0.5 mg/kg, 5 mg/kg, or 50 mg/kg was administered orally, once daily for 4 weeks. Kruskal–Wallis test followed by Mann–Whitney U test were used for statistical evaluation of loratadine effect in comparison with the control rats. *P<0.05, **P<0.01 – in comparison with the control rats.

Abbreviations: C, control rats; L0.5, rats treated with loratadine at a dose of 0.5 mg/kg p.o.; L5, rats treated with loratadine at a dose of 5 mg/kg p.o.; L50, rats treated with loratadine at a dose of 50 mg/kg p.o.

Table 3 Effects of loratadine (0.5–50 mg/kg p.o.) on histomorphometric parameters of the distal metaphysis, diaphysis, and distal epiphyseal cartilage in the femur in young male rats

Parameter/group		C	L0.5	L5	L50
Metaphysis	BV/TV (%)	37.4 (31.7–48.6)	40.9 (32.1–47.2)	38.0 (31.2–49.7)	40.0 (28.5–54.7)
	Tb.Th (μm)	55.5 (52.1–78.8)	62.9 (49.4–67.4)	64.2 (54.5–72.0)	59.1 (51.1–74.5)
	Tb.Sp (μm)	108.4 (66.1–112.1)	94.1 (74.8–104.9)	112.9 (72.0–128.5)	90.6 (54.4–128.1)
	Tb.N (mm^−1)	6.10 (5.37–7.78)	6.68 (6.00–7.13)	5.60 (5.19–7.70)	6.72 (5.58–8.33)
Diaphysis	Ct.Ar (mm^2)	4.30 (4.01–4.74)	4.40 (3.97–4.77)	4.22 (3.89–4.67)	4.08 (3.62–4.76)
	Ma.Ar (mm^2)	3.90 (3.19–4.73)	3.97 (3.46–5.13)	3.91 (3.59–5.19)	3.95 (3.61–4.53)
	Ma.Ar/Tt.Ar	0.476 (0.443–0.503)	0.485 (0.442–0.553)	0.485 (0.446–0.552)	0.492 (0.441–0.509)
	Ps.MAR (µm/day)	6.37 (3.17–8.02)	5.11 (3.96–8.36)	5.79 (5.15–6.60)	6.02 (4.94–8.03)
	Es.MAR (µm/day)	4.45 (3.15–5.69)	3.73 (2.82–7.19)	5.37 (3.14–6.20)	4.56 (3.71–6.24)
Epiphyseal cartilage	Reserve zone width (μm)	38.1 (28.7–40.5)	40.1 (34.0–41.5)	39.3 (31.9–48.5)	36.6 (30.5–41.6)
	Proliferative zone width (μm)	50.1 (45.1–53.2)	48.8 (38.8–57.9)	52.8 (41.7–55.5)	44.8 (42.0–52.2)
	Hypertrophic zone width (μm)	39.6 (33.9–45.0)	42.0 (33.3–43.9)	41.6 (37.4–47.3)	37.0 (34.0–39.1)

Notes: Results are presented as median (min–max); n=8–10. Loratadine at doses of 0.5 mg/kg, 5 mg/kg, or 50 mg/kg was administered orally, once daily for 4 weeks. Kruskal–Wallis test followed by Mann–Whitney U test were used for statistical evaluation of loratadine effect in comparison with the control rats.

Abbreviations: BV/TV, bone volume/tissue volume ratio; C, control rats; Ct.Ar, transverse cross-sectional area of the cortical bone; Es.MAR, endosteal mineral apposition rate; L0.5, rats treated with loratadine at a dose of 0.5 mg/kg p.o.; L5, rats treated with loratadine at a dose of 5 mg/kg p.o.; L50, rats treated with loratadine at a dose of 50 mg/kg p.o.; Ma.Ar, transverse cross-sectional area of the marrow cavity; Ma.Ar/Tt.Ar, transverse cross-section of the marrow cavity/total diaphysis area ratio; Ps.MAR, periosteal mineral apposition rate; Tb.N, trabecular number; Tb.Sp, trabecular separation; Tb.Th, trabecular thickness.

Table 4 Effects of loratadine (0.5–50 mg/kg p.o.) on mechanical properties of the tibial metaphysis in young male rats

Parameter/group	C	L0.5	L5	L50
Young’s modulus (MPa)	577 (428–862)	560 (447–915)	662 (559–961)	861 (452–1010)
Maximum load (N)	36.1 (29.2–38.5)	34.4 (28.4–38.2)	32.4 (27.6–44.1)	43.0 (30.6–62.2)
Displacement for maximum load (mm)	0.922 (0.642–1.971)	1.081 (0.713–2.007)	1.211 (0.700–1.735)	1.319 (0.591–2.001)
Energy for maximum load (mJ)	21.0 (13.0–50.0)	24.5 (14.0–57.0)	26.0 (13.0–49.0)	37.0 (13.0–61.0)
Stress for maximum load (MPa)	19.0 (13.5–23.8)	18.2 (15.2–22.1)	19.1 (13.8–25.7)	23.1 (16.0–33.8)
Fracture load (N)	27.3 (23.2–35.5)	31.0 (20.2–36.4)	29.0 (26.8–34.6)	34.4 (27.0–42.3)
Displacement for fracture load (mm)	2.001 (1.476–2.006)	2.002 (1.585–2.007)	2.001 (1.498–2.004)	2.001 (1.713–2.002)
Energy for fracture load (mJ)	51.0 (42.0–56.0)	52.0 (37.0–61.0)	51.0 (46.0–63.0)	63.0 (47.0–84.0)
Stress for fracture load (MPa)	15.1 (11.5–23.4)	16.3 (10.7–22.1)	15.9 (13.7–19.8)	17.5 (15.8–22.9)

Notes: Results are presented as median (min–max); n=8–10. Loratadine at doses of 0.5 mg/kg, 5 mg/kg, or 50 mg/kg was administered orally, once daily for 4 weeks. Kruskal–Wallis test followed by Mann–Whitney U test were used for statistical evaluation of loratadine effect in comparison with the control rats.

Abbreviations: C, control rats; L0.5, rats treated with loratadine at a dose of 0.5 mg/kg p.o.; L5, rats treated with loratadine at a dose of 5 mg/kg p.o.; L50, rats treated with loratadine at a dose of 50 mg/kg p.o.