International Journal of Endocrinology

Research Article

Atypical Femoral Fracture in Hypophosphatasia: A Systematic Review

Table 1

Characteristics of reported patients with hypophosphatasia and atypical femoral fracture.


Patient no	Study	Year	Country	Age, sex	Type of HPP	Antiosteoporosis medication exposure	Unilateral/Bilateral	Other fracture(s)	ALPL variants	Medical treatment after AFF

1	Anaraki et al. [15]	2018	US	76F	adultHPP	AL (4 years), TPT (1 year), AL&ZA (3 years), ZA (3 years), DMAB (1 dose), TPT (1 year), followed by DMAB	Unilateral	Right wrist, right metatarsal, right knee cap, left metatarsal and lumbar spine fractures	N/A	—
2	Bhadada et al. [16]	2020	India	47F	adultHPP	—	Bilateral	—	Heterozygous: c.311A > G (p.Asn104Ser)	—
3	Buklemishev and Rodionova [17]	2020	Russia	40M	childhoodHPP	—	Bilateral	—	Compound heterozygous: c.182G > A (p.Gly61Glu), c.571G > A (p.Glu191lys)	AA and alfacalcidol
4	Chittimala et al. [18]	2020	US	56M	adultHPP	—	Bilateral	—	N/A	—
5	Coe et al. [19]	1986	US	67F	adultHPP	—	Bilateral	—	N/A	—
6	Coe et al. [19]	1986	US	61F	adultHPP	—	Unilateral	—	N/A	—
7	Coe et al. [19]	1986	US	66F	adultHPP	—	Bilateral	—	N/A	—
8	Coe et al. [19]	1986	US	69F	adultHPP	—	Bilateral	—	N/A	—
9	Coe et al. [19]	1986	US	45M	adultHPP	—	Unilateral	—	N/A	—
10	Doshi et al. [20]	2009	US	53F	adultHPP	RIS	Bilateral	—	N/A	TPT
11	Fanous and Barb [21]	2020	US	49F	adultHPP	—	Unilateral	Multiple metatarsal stress fractures and a rib fracture	Heterozygous: c.407G > A (p.Arg136His)	AA
12	Gagnon et al. [22]	2010	Australia	53F	adultHPP	—	Bilateral	Wrist and thoracic vertebral fractures	Compound heterozygous: c.526G > A (p.Ala176Thr), c.1268T > C (Val423Ala)	TPT
13	Klidaras et al. [23]	2018	US	41F	adultHPP	—	Bilateral	Rib and left tibial fractures	Compound heterozygous: c.526G > A (p.Ala176Thr), c1132G > C (p.Asp378His)	AA
14	Laurent et al. [24]	2017	France	69F	childhoodHPP	RIS (6 y) followed by DMAB	Unilateral	Wrist, metatarsal and tibial fractures	Heterozygous: c.361G > A (p.Val121Met)	—
15	Lawrence et al. [25]	2017	UK	55F	adultHPP	—	Bilateral	Right tibia and 4^th and 5^th metatarsal fractures	Compound heterozygous: c.526G > A p.(Ala176Thr), c.1171C > T p.(Arg391Cys)	—
16	Lefever et al. [26]	2020	Belgium	36F	adultHPP	BP and/or DMAB	N/A	—	Homozygous: c.896T > C (p.Leu299Pro)	—
17	Lefever et al. [26]	2020	Belgium	69F	adultHPP	BP and/or DMAB	N/A	—	Homozygous: c.896T > C (p.Leu299Pro)	—
18	Maman et al. [27]	2016	France	51M	adultHPP	—	Bilateral	Multiple metatarsal fractures	Compound heterozygous: T (p.Thr100Met), c.571G > A (p.Glu191Lys)	—
19	Miller et al. [28]	2017	US	61M	adultHPP	TPT (6 m)	Bilateral	—	Compound heterozygous: A (p.Pro292Thr), c.1195G > A (p.Ala399Thr)	AA
20	Resch et al. [29]	2016	Austria	25M	adultHPP	—	N/A	—	N/A	—
21	Righetti et al. [30]	2017	France	67F	adultHPP	AL	Bilateral	Fibular, ankle, and metatarsal fractures	Heterozygous: c.341C > T (p.Ala114Val)	TPT
22	Schalin-Jantti et al. [31]	2010	France	56F	adultHPP	—	Bilateral	Metatarsal fractures	Compound heterozygous: c.1015G > A (p.Gly339Arg), c.571G > A (p.Glu191Lys)	TPT
23	Schalin-Jantti et al. [31]	2010	France	64F	adultHPP	—	Unilateral	—	Compound heterozygous: c.1015G > A (p.Gly339Arg), c.571G > A (p.Glu191Lys)	TPT
24	Schini and Eastell [32]	2018	UK	48F	adultHPP	AL	Bilateral	2 metatarsal fractures	—	—
25	Siami et al. [33]	2022	Iran	30F	adultHPP	—	Bilateral	—	—	—
26	Sutton et al. [34]	2012	Canada	55F	adultHPP	AL followed by ZA	Bilateral	Left lower tibia stress periostosis, right 2^nd metatarsal, left 2^nd and 3^rd metatarsal, right distal radius, right distal ulna and right talus avulsion fractures	Heterozygous: A (p.Arg71His)	—
27	Warren et al. [35]	2021	Australia	40F	adultHPP	DMAB	Bilateral	Left navicular and 3^rd and 5^th metatarsal fractures	Compound heterozygous: A (p.Ala176Thr), c.881A > C (p.Asp294Ala)	TPT
28	Whyte et al. [36]	2007	US	56F	adultHPP	—	Unilateral	Right 4^th and 5^th metatarsal and left 5^th metatarsal stress fractures	Heterozygous: T (p.Asp378Val)	TPT

Abbreviations: AA: asfotase alfa; AL: alendronate; BP: bisphosphonate; DMAB: denosumab; F: female; M: male; N/A: not available; RIS: risedronate; TPT: teriparatide; UK: the United Kingdom; US: the United States; ZA: zoledronic acid.