Table 4.

Occurrence of HPP-related symptoms and tamoxifen treatment: comparison between patients harboring the pathogenic/likely-pathogenic variants, the benign/likely benign variants and the wild-type alleles of ALPL gene

Risk factors	Pathogenic ALPL variants	Benign ALPL variants	Wild-type ALPL alleles	P value
Dental anomalies (%)	4/1 (80)*	3/5 (38)	0/9 (0)	0.023
Neurologic and musculoskeletal symptoms (%)	2/3 (40)	4/4 (50)§	0/9 (0)	0.027
Mineral metabolism anomalies (%)	1/4 (20)	5/3 (63)#	0/9 (0)	0.014
Familiarity for osteoporosis and/or fragility fractures (%)	3/2 (60)	5/3 (71)	1/8 (10)	0.061
All fractures (%)	4/1 (80)°°	5/3 (57)°	1/8 (20)	0.022
Vertebral fractures (%)	4/1 (80)	3/5 (37)	1/8 (20)	0.037
Increased urine PEA and/or serum PLP	5/0 (100)	6/2 (75)	5/4 (55)	0.199
Six-points score (mean ± SEM)	4.0 ± 0.6	3.4 ± 0.5	0.8 ± 0.2	0.0001
Tamoxifen treatment (%)	0/5 (0)$$	1/7 (13)$	6/3 (67)	0.013

Dental anomalies: recurrent caries (n = 3), early loss of permanent dental elements (n = 4), periodontal disease (n = 1); musculoskeletal and mineral metabolism symptoms: scoliosis (n = 1), dorsal hyperkiphosis (n = 2), osteoarthropathy and muscular pain (n = 4), seizure (n = 1); mineral metabolism anomalies: kidney stones (n = 3), hypercalciuria (n = 4); familiarity: first degree relatives with osteoporosis and/or fragility fractures; fractures: vertebral fractures (n = 8), ribs (n = 2), distal radius (n = 1), humerus (n = 1), clavicle (n = 1). Dicotomic variables are presented as the number of patients experiencing the indicated risk factor/number of patients free from the indicated risk factor; variables were compared by the Chi-Square test; 6-point scores are presented as mean ± SEM and they were analyzed by one-way ANOVA

Bold values indicate statistically significant P values

*P = 0.017 versus wild-type ALPL variants (WT)

^§P = 0.029 versus WT

^#P = 0.009 versus WT

°P = 0.049 versus WT

°°P = 0.023 versus WT

^$P = 0.049 versus WT

^$$P = 0.031 versus WT