Non-nutritional rickets: Approach, precision medicine, and outcomes

Table 2 Monitoring in X-linked hypophosphatemic rickets

Domain	Assessment	Suggested frequency	Key considerations
Clinical evaluation	Growth (height, weight, BMI)	At every visit in children; 6-12 monthly in adults	Monitor growth velocity and disproportion
	Limb deformities, gait, bone pain	Every visit	Assess progression and need for orthopedic referral
	Head shape, craniosynostosis signs	Regular in early childhood	Neuro symptoms warrant imaging
	Dental evaluation	Every 6 months after tooth eruption	High risk of abscesses and periodontal disease
	Hearing assessment	From approximately 8 years or if symptomatic	Sensorineural hearing loss may occur
	Functional status (mobility, fatigue)	Annually or as indicated	Include 6-minute walk test where feasible
Biochemical monitoring	Serum calcium, phosphate, ALP, PTH, creatinine	Every 3-6 months (more frequent in active treatment)	ALP is a key marker of disease activity
	25-hydroxyvitamin D	Yearly	Maintain sufficiency
	1,25-dihydroxyvitamin D	Annually (especially on targeted therapy)	Avoid excess contributing to hypercalciuria
	Urinary calcium (spot Ca/Cr or 24 hours)	Every 3-6 months	Monitor for hypercalciuria
	TmP/GFR and serum phosphate	Frequent during treatment initiation (2-4 weekly), then spaced	Especially important with burosumab
Imaging	Radiographs (wrists/knees/long bones)	Every 1-2 years or if clinically indicated	Assess rickets healing and deformity
	Renal ultrasonography	Every 1-2 years	Detect nephrocalcinosis
	Dental imaging (OPG/CBCT)	From approximately 6 years, based on need	Detect occult dental pathology
	Brain MRI	If neurological symptoms or craniosynostosis suspected	Not routine
	Spine MRI	If symptoms of stenosis or back pain	Targeted imaging only
Cardiovascular	Blood pressure	At least annually	Hypertension may occur
	Echocardiography	If persistent hypertension	Not routine screening
Treatment monitoring	Clinical + biochemical response	Every 3-6 months initially	Adjust therapy based on trends, not single values
	Adverse effects (nephrocalcinosis, hyperparathyroidism)	Ongoing	Especially with phosphate + active vitamin D
Quality of life	Quality of life assessment tools	Every 1-2 years	Particularly in older children and adults

BMI: Body mass index; ALP: Alkaline phosphatase; PTH: Parathyroid hormone; Ca: Calcium; Cr: Creatinine; TmP: Tubular maximum reabsorption of phosphate; GFR: Glomerular filtration rate; OPG: Orthopantomogram; CBCT: Cone beam computed tomography; MRI: Magnetic resonance imaging.