Table 2.

Brittle nail syndrome studies

Study	Design	Therapy	Dosage	Sample size	Patient demographics (age/sex)	Nail involvement	Outcomes
Floersheim et al. (1989) [22]	Clinical trial	Oral biotin	2.5 mg/day	45 patients	NR	Fingernails	Improved firmness and hardness of fingernails in 41/45 patients (91%) following a 5.5±2.3-month course of therapy. Nail brittleness and ridging returned 10 weeks after biotin discontinuation.
Colombo et al. (1990) [23]	Clinical trial	Oral biotin	2.5 mg/day	22 patients	NR	Fingernails	In the group of BNS patients from whom nail samples were obtained before and after biotin administration (8 nails), nail thickness increased by 25% from 256±53 μm to 319±86 μm (p < 0.05) as assessed by scanning electron microscopy after 9.6±3.6 months of oral biotin.
Hochman et al. (1993) [24]	Retrospective study	Oral biotin	2.5 mg/day	46 patients	Median age 57 years (21–74); sex NR	NR	Patient reported clinical improvement in nails after 1–4 months (average 2 months) in 22 out of 35 (63%) patients.
Piraccini et al. (2005) [25]	Case series	Oral biotin	Oral biotin 5 mg/day and 10% urea ointment once-twice daily	14 patients	Mean age 42.9 years (32–56); 12 female patients and two male patients	Triangular worn-down nails	At 6 months, clinical improvement and complete clinical resolution was achieved in 6/9 (66.7%) and 3/9 (33.3%) patients, respectively. At 1 year of therapy, 9/9 (100%) of patients had complete resolution. Recurrences occurred in three patients thereafter.
Chiavetta et al. (2019) [26]	Clinical trial	Oral biotin	Hydroxypropyl chitosan-based nail lacquer (HPC-NL) nail lacquer group (once daily); HPC-NL nail lacquer once daily and oral biotin 10 mg daily	50 patients	Mean age 64±11 years; 21 male patients and 29 female patients	Toenails	At 4 months, proportion of patients with an onychodystrophy global severity score reduction of greater than 50% compared to baseline was 53 and 80% in the nail lacquer arm and combination regimen arm, respectively (p = 0.05).
Sparavigna et al. (2019) [27]	Clinical trial	Topical biomineral formulation (cystine, panthenol, vitamin E); Oral biomineral formulation (L-cystine, L-arginine, glutamic acid, vitamin C, vitamin E, vitamin B6, vitamin B7, zinc, iron, copper); Combination of topical biomineral formulation and oral biomineral supplement	Topical biomineral formulation; oral biomineral formulation; topical and oral biomineral formulation (dosage NR)	50 patients	Mean age 39–45 years (18–54); 50 female patients and 0 male patients	Fingernails	At 3 months, nail hardness improved by 40% in the topical arm (p < 0.01), 43% in the oral arm (p < 0.05), and 50% in the combination arm (p < 0.05). Nail roughness decreased by 12% in the topical arm (p < 0.05), 18% in the oral arm (p < 0.05), and 15% in the combination arm (p < 0.05).
Sherber et al. (2011) [28]	Clinical trial	Topical tazarotene	Topical tazarotene cream 0.1% twice daily	20 patients	Mean age 65.7±6.67 years (55–76); sex NR	Fingernails	After 12 weeks therapy and at 12-week post-therapy follow-up, 100% of patients (18/18) achieved assessment score of target nails.