X-Linked Hypophosphatemia: The Inherited Phosphate-Wasting Rickets

Table of Contents

1. X-Linked Hypophosphatemia in Brief
2. The PHEX Gene and the X-Linked Pattern
3. How a Bone Hormone Drains Phosphate and Lowers Active Vitamin D
4. Signs in Children
5. Signs in Adults
6. How the Diagnosis Is Made
7. Conventional Treatment: Oral Phosphate Plus Active Vitamin D
8. Burosumab: An Antibody Against the Phosphate-Wasting Hormone
9. What the United States Label States
10. What the 2019 Clinical Practice Recommendations State
11. What Is Not Known
12. Key Research Papers
13. Connections
14. Featured Videos

X-Linked Hypophosphatemia in Brief

Phosphate is one of the two minerals, with calcium, that turn the soft protein framework of new bone into hard bone. A child's growth plates and an adult's constantly renewed bone both need a steady supply of it. In X-linked hypophosphatemia that supply runs short for life, not because the diet lacks phosphate but because the kidneys keep throwing it away.

A 2011 clinician's guide written after a United States National Institutes of Health conference on rare bone diseases called X-linked hypophosphatemia “the prototypic disorder of renal phosphate wasting, and the most common form of heritable rickets” (Carpenter 2011). The 2019 clinical practice recommendations describe it in the same terms, as the most common cause of inherited phosphate wasting (Haffner 2019).

The condition is rare. A 2023 survey of children's doctors in Australia and New Zealand notes that published prevalence figures range between 1 in 20,000 and 1 in 200,000 people. That survey found 75 children with the condition in Australia and 18 in New Zealand, giving an estimated minimum prevalence of 1.33 per 100,000 in Australia and 1.60 per 100,000 in New Zealand; the authors judged the true figure likely higher because not every case was reported (Sandy 2023).

Three features shape the rest of this page:

• It is lifelong. The adult trial report describes the kidney phosphate wasting as lifelong (Insogna 2018).
• It affects many body systems. Bones, joints, teeth, tendons, the ears and the parathyroid glands are all involved, which is why the 2019 recommendations describe care by teams led by a metabolic bone disease expert (Haffner 2019).
• It is often recognised late. The 2019 recommendations state that diagnosis and specific treatment are frequently delayed because of the condition's rarity, and that the delay harms outcomes (Haffner 2019).

The PHEX Gene and the X-Linked Pattern

In 1995 an international research group called the HYP Consortium used a gene-mapping method (positional cloning) to find the gene behind the condition in a region of the X chromosome labelled Xp22.1. The gene looked like members of a family of enzymes called endopeptidases, which cut and so switch on or switch off various peptide hormones. They found deletions inside the gene in four unrelated families and three further changes in other patients, and named it PEX (HYP Consortium 1995). Today it is known as PHEX, short for “phosphate-regulating endopeptidase homolog, X-linked” (Imel 2019).

The condition comes from changes that stop the PHEX gene working (loss-of-function variants). The adult trial report summarises the chain: inherited loss-of-function mutations in PHEX cause excess circulating fibroblast growth factor 23 (FGF23), which leads to lifelong kidney phosphate wasting and low blood phosphate (Insogna 2018).

Most families carry their own variant. In a Spanish study of 43 affected people from 36 unrelated families, PHEX changes were found in every patient; 69.4% of the variants had never been described before, and most were specific to one family (Morey 2011). In a French adult clinic, a PHEX variant was found in 105 of 114 patients (94.6%) (Herrou 2022).

How the X-linked pattern works. The children's phase 3 trial describes the condition as following X-linked dominant inheritance (Imel 2019), and the 1995 gene report calls it a dominant disorder (HYP Consortium 1995). “Dominant” means one altered copy of the gene is enough to cause the condition. “X-linked” means the gene sits on the X chromosome. A father passes his X chromosome to every daughter and to none of his sons, so a father with the condition passes it to his daughters but not to his sons. A mother passes one of her two X chromosomes to each child, so both sons and daughters can inherit it from her.

Not every child has an affected parent. In the Australian and New Zealand survey most children had a family history, but some cases were sporadic (new in the family), and late diagnosis was more common in the sporadic cases than in the familial ones (Sandy 2023).

How a Bone Hormone Drains Phosphate and Lowers Active Vitamin D

Fibroblast growth factor 23 is a hormone made in bone that tells the kidneys how much phosphate to keep. The general physiology is laid out on the Phosphorus for Bone Mineralization page. In X-linked hypophosphatemia the problem is that there is too much of this hormone. The children's trials describe the condition as characterised by elevated or increased fibroblast growth factor 23, leading to low blood phosphate, rickets, leg bowing and impaired growth (Imel 2019; Carpenter 2018).

Two effects on the kidney. A 2004 animal study showed both effects of the hormone directly. When researchers injected fibroblast growth factor 23 into rats and mice:

• Blood levels of active vitamin D (1,25-dihydroxyvitamin D, also called calcitriol) had already fallen at 3 hours and reached their lowest point at 9 hours. The hormone lowered the kidney's message for the enzyme that activates vitamin D and raised the message for the enzyme that breaks it down, starting within 1 hour.
• Blood phosphate first fell at 9 hours, along with lower levels of the main kidney phosphate transporter (the sodium-phosphate cotransporter NaPi-2a), which normally pulls phosphate back from the urine.
• The phosphate drop also happened in rats whose parathyroid glands had been removed, so it did not depend on parathyroid hormone (Shimada 2004).

Why the vitamin D finding matters. Normally, when blood phosphate is low, the kidney makes more active vitamin D to absorb more phosphate from food. In inherited hypophosphatemic rickets that response is missing: these conditions are defined by kidney phosphate wasting with “inappropriately low or normal” active vitamin D levels (Morey 2011). The body is short of phosphate on two fronts at once — more lost in the urine and less taken in from the gut.

The result in bone. Without enough phosphate, newly laid bone cannot harden properly. In a growing child this shows at the growth plates as rickets; in an adult it shows as osteomalacia, with soft bone, pain and incomplete fractures (Carpenter 2018; Insogna 2018).

Signs in Children

The 2019 recommendations list rickets, lower-limb deformities, pain, poor mineralisation of the teeth and disproportionate short stature as the main complications in children (Haffner 2019).

The Australian and New Zealand survey gives a picture of what doctors actually saw. Among the children with data:

• Leg bowing was recorded in 89%, bone and joint pain in 68%, an abnormal walk in 57% and short stature in 49%.
• 49% were diagnosed after 2 years of age, even though most had a family history.
• 41% had dental problems such as tooth abscesses, dental capping or extractions, yet only 68% were seeing a dentist and 3% a psychologist.
• Nephrocalcinosis (calcium deposits in the kidneys) was recorded in 32% and hyperparathyroidism (overactive parathyroid glands) in 20%; both are discussed under treatment below.
• The survey also recorded a heavy burden of orthopaedic disease and surgery (Sandy 2023).

Tooth abscesses without decay. A distinctive dental feature is an abscess in a tooth that looks healthy from the outside. An Italian study compared dental X-rays of 24 children with the condition (average age 5.8 years) with healthy children of the same age and sex. The children with X-linked hypophosphatemia had larger pulp chambers (the soft centre of the tooth that holds nerves and blood vessels), with pulp horns reaching further up into the crown. Sixteen of the 24 children (67%) had a history of abscesses, most often in the incisors. The children with abscesses had more severe rickets, higher parathyroid hormone and lower active vitamin D than those without, and the specific PHEX variant did not predict the dental picture (Baroncelli 2021).

Signs in Adults

The adult phase 3 trial report lists the problems adults live with: chronic muscle and bone pain and stiffness, short stature, deformed legs, fractures and pseudofractures (partial cracks in the bone, also called Looser zones) caused by osteomalacia, early wear-and-tear arthritis (accelerated osteoarthritis), dental abscesses and enthesopathy (Insogna 2018). The 2019 recommendations add hyperparathyroidism to the adult list (Haffner 2019).

Enthesopathy. An enthesis is the spot where a tendon or ligament attaches to bone. In X-linked hypophosphatemia these attachment points can harden and grow bony spurs, which stiffens the spine, hips and other joints. A French reference centre reviewed whole-body X-rays of 114 adults (mean age 42.2 years; 77.5% treated in childhood) and found enthesopathies of the spine and/or pelvis in 67% (76 patients). People with enthesopathies were older and had more severe dental disease, measured as more missing teeth, more root-canal-treated teeth, more bone loss around the teeth and more people with five or more abscesses. The PHEX variant did not predict who had them. The authors describe enthesopathies as the determinant of poor quality of life in adults with the condition (Herrou 2022).

Hearing loss. A 2025 review of 12 studies found reports of hearing loss in 13% to 76% of adults with X-linked hypophosphatemia, more often of the inner-ear (sensorineural) type, developing in adulthood, affecting high and low pitches and sometimes fluctuating. Proposed causes are thickening of the skull bone around the ear, softening of the tiny hearing bones (the ossicles) and a build-up of inner-ear fluid called endolymphatic hydrops; the review states that the cause is incompletely understood (Oh 2025).

Spinal stenosis. The burosumab label states that narrowing of the spinal canal (spinal stenosis) is prevalent in adults with X-linked hypophosphatemia and that spinal cord compression has been reported; in the drug's adult phase 2 and phase 3 studies, 7 of 176 patients had spinal surgery, mostly for stenosis that was already present (US label).

Daily life and mood. A 2021 systematic review of the adult burden found skeletal deformities, fractures and pseudofractures, pain, dental problems and reduced physical function and mobility, with effects on quality of life and daily activities, and concluded that adults may not receive appropriate care, possibly because of low awareness among health professionals (Seefried 2021). A United Kingdom primary-care records study matched 64 patients with the condition against 256 people without it and found higher rates of endocrine and neurological diagnoses; of all the individual conditions examined, only depression passed the study's strict statistical threshold, with odds of 2.95 times those of the comparison group (Hawley 2021).

How the Diagnosis Is Made

The 2019 recommendations state that the diagnosis is based on signs of rickets and/or osteomalacia together with low blood phosphate and kidney phosphate wasting, in the absence of vitamin D or calcium deficiency. They add that, whenever possible, the diagnosis is confirmed before treatment by a genetic test or a measurement of fibroblast growth factor 23 (Haffner 2019).

The usual pieces of the work-up are:

• Blood phosphate. The trials enrolled patients by low phosphate: the children's phase 3 trial required a fasting serum phosphorus below 3.0 mg/dL (0.97 mmol/L) (Imel 2019). Normal ranges depend on age, and the burosumab label refers to “the reference range for age” (US label); the children's phase 2 trial used 3.2 to 6.1 mg/dL as its normal range (Carpenter 2018).
• Kidney phosphate handling. Paired blood and urine samples show whether the kidneys are holding on to phosphate or spilling it. One common calculation is the tubular maximum reabsorption of phosphate per glomerular filtration rate (TmP/GFR), often called the kidney phosphate threshold; another is the percentage of filtered phosphate reabsorbed. In the Spanish cohort, people with clearly damaging PHEX variants had lower reabsorption (61.39% on average) than those with variants classed only as likely causative (80.14%) (Morey 2011).
• Active vitamin D. Low or normal levels, when the body “ought” to be making more, point toward a hormone-driven cause (Morey 2011).
• Fibroblast growth factor 23. The 2019 recommendations name a blood measurement of fibroblast growth factor 23 as one way to confirm the diagnosis (Haffner 2019).
• Genetic testing. Sequencing the PHEX gene confirms the diagnosis and allows family members to be tested (Haffner 2019; Morey 2011).
• X-rays. The trials scored rickets on X-rays using a severity scale running from 0 to 10 (the Thacher rickets severity score) and a global scale of change (Carpenter 2018; Imel 2019).

How it differs from vitamin D deficiency rickets. Rickets caused by a lack of vitamin D or calcium (nutritional rickets) is described by the 2016 global consensus on that condition as preventable, and the consensus calls for prevention programmes that include supplementation and food fortification (Munns 2016). X-linked hypophosphatemia is diagnosed precisely when vitamin D and calcium deficiency are absent (Haffner 2019). Both produce rickets, but they differ in cause: one is a shortage of vitamin D or calcium, the other a kidney phosphate leak driven by a bone hormone, often running in the family. The nutritional form is covered on the Rickets in Children page, and the adult forms of soft bone on the Bone Pain and Osteomalacia and Bone Pain and Softening pages.

Other causes of a hormone-driven phosphate leak exist. Among them is a rare acquired form in adults, tumour-induced osteomalacia, in which a tumour makes the hormone; the burosumab label covers that condition separately (US label). Iron given into a vein can also lower phosphate through the same hormone, a topic on the Intravenous Iron and Low Phosphate page.

Conventional Treatment: Oral Phosphate Plus Active Vitamin D

For decades the standard treatment has been phosphate salts by mouth together with an active form of vitamin D such as calcitriol (Imel 2019). A 2019 paper from a United States centre describes the regimen as requiring “high doses of phosphate salts combined with active vitamin D analogues,” and lists its risks as nephrocalcinosis and secondary hyperparathyroidism, with possible progression to tertiary (high-calcium) hyperparathyroidism (DeLacey 2019). The abstracts read for this page do not give a single standard dose.

Kidney calcium deposits. A 1995 ultrasound study asked whether nephrocalcinosis comes from the disease or from the treatment. Among 14 patients who had never been treated (10 adults and 4 children), none had nephrocalcinosis. Among 18 treated patients (10 adults and 8 children), 5 adults and 5 children had it. Phosphate dose, but not vitamin D dose, differed significantly between treated patients with and without the deposits, and the authors concluded that the findings point to a convincing role for medical therapy (Taylor 1995). A 2025 meta-analysis found nephrocalcinosis in 29% (151 of 517) of patients in studies that reported it (Fisch 2025).

Overactive parathyroid glands. The parathyroid glands respond to swings in phosphate and calcium, and in X-linked hypophosphatemia they often become overactive:

• In a United States centre's records, 70 of 84 patients (83.3%) with paired calcium and parathyroid hormone measurements had secondary or tertiary hyperparathyroidism at some point; tertiary hyperparathyroidism was found in 14 of 84 (16.7%). Of 8 who had parathyroid surgery, 6 had persistent or recurrent tertiary disease. Nephrocalcinosis was more common with tertiary disease (60.0%) than without it (18.6%). The authors concluded that most patients develop secondary hyperparathyroidism during treatment with phosphate and active vitamin D (DeLacey 2019).
• In a French study of 68 adults compared with 136 matched healthy volunteers, 17 patients (25%) had hyperparathyroidism and 7 (10%) had the high-calcium form; all 7 had surgery, after which calcium and parathyroid hormone returned to normal (Lecoq 2020).
• A 2025 meta-analysis pooled a tertiary hyperparathyroidism prevalence of 9.0% across nine studies (583 patients) and a secondary hyperparathyroidism prevalence of 34% across five studies (298 patients). Most included studies involved conventional therapy or no treatment, two included patients on burosumab, and tertiary prevalence did not differ by treatment type (Fisch 2025).

Dental and joint outcomes. In the Italian dental study, all 24 children were on conventional treatment, for an average of 3.5 years, and 67% had a history of abscesses (Baroncelli 2021). In the French adult study, 77.5% had been treated in childhood, and enthesopathies were still found in 67% (Herrou 2022). Neither study was designed to test whether treatment changes these outcomes.

Burosumab: An Antibody Against the Phosphate-Wasting Hormone

Burosumab is a fully human monoclonal antibody that binds fibroblast growth factor 23 and blocks it, so the kidneys can hold on to phosphate again; in the long-term adult study, active vitamin D levels rose as well (Insogna 2018; Imel 2019; Kamenicky 2023). It is given as an injection under the skin. The children's trials were funded by the drug's developers, and developer employees are among the authors of the adult trial reports.

Children: the phase 2 dose-finding trial

In an open-label phase 2 trial, 52 children with X-linked hypophosphatemia were randomly assigned to burosumab every 2 weeks or every 4 weeks, with the dose adjusted to bring blood phosphorus to the low end of normal. The average rickets severity score fell from 1.9 to 0.8 by week 40 with every-2-week dosing and from 1.7 to 1.1 with every-4-week dosing, and the improvements held at week 64. Blood phosphorus rose after the first dose, and more than half of the children in both groups were in the normal range (3.2 to 6.1 mg/dL) by week 6. Average alkaline phosphatase, a marker of active rickets, fell from 459 to 369 U per litre by week 64. Height scores improved more with every-2-week dosing (up 0.19 standard deviation scores at week 64) than with every-4-week dosing (up 0.12). Physical ability improved, pain decreased and nearly all adverse events were mild or moderate (Carpenter 2018).

Children: the phase 3 trial against conventional therapy

The key comparison came in a randomised, open-label phase 3 trial at 16 sites. It enrolled 61 children aged 1 to 12 with confirmed PHEX variants who had already been on conventional therapy for at least 6 months (under age 3) or 12 months (age 3 and over). Twenty-nine switched to burosumab, starting at 0.8 mg/kg every 2 weeks, and 32 continued oral phosphate and active vitamin D; both arms lasted 64 weeks.

• Rickets healing at week 40 (the main outcome, scored on X-rays): +1.9 with burosumab against +0.8 with conventional therapy, a difference of 1.1.
• Other outcomes: the authors report greater improvement in rickets severity, growth and blood chemistry with burosumab.
• Side effects judged possibly, probably or definitely treatment-related: 17 of 29 children (59%) on burosumab against 7 of 32 (22%) on conventional therapy.
• Serious adverse events: three in each group, all judged unrelated to treatment, and all resolved (Imel 2019).

The trial was open-label, meaning families and doctors knew which treatment each child received; the X-ray scoring was the main outcome.

Adults: the placebo-controlled phase 3 trial

In a double-blind trial, 134 adults with low phosphate and pain received burosumab 1 mg/kg (68 people) or a placebo (66 people) every 4 weeks.

• Blood phosphate: across the middle of the dosing intervals, 94.1% on burosumab reached an average level above the lower limit of normal, against 7.6% on placebo.
• Stiffness: burosumab significantly reduced stiffness on a standard arthritis questionnaire. The improvements in physical function and worst pain did not reach statistical significance after correction for multiple comparisons.
• Fractures and pseudofractures: at week 24, 43.1% of the cracks that were active at the start had fully healed with burosumab, against 7.7% with placebo; the odds of healing were 16.8-fold greater.
• Safety: the authors describe the safety profile as similar to placebo, with no treatment-related serious adverse events and no meaningful changes in blood or urine calcium, parathyroid hormone or nephrocalcinosis (Insogna 2018).

Adults: longer follow-up

After the 24-week blinded period, all participants received burosumab every 4 weeks up to week 96. By week 48 all stiffness, function and pain scores had improved significantly from the start, and by week 96 fatigue scores had too; walking distance on a six-minute walk test improved significantly at every time point from week 24 (Briot 2021). In a further 48-week extension, 31 participants kept their gains in blood phosphate, active vitamin D, kidney phosphate reabsorption, pain, stiffness, fatigue and walking. Between the two studies there was a gap of 6 to 18 months, during which some, but not all, received the drug on compassionate grounds; a post-hoc exploratory analysis of the 7 who stopped suggested the benefits may be lost when treatment is interrupted and recover when it is restarted. The authors concluded that continued treatment appears necessary for sustained benefit (Kamenicky 2023).

What the United States Label States

The label for burosumab (initial United States approval 2018; version published on DailyMed July 2026) gives the following. Questions about any individual's treatment are for the treating specialist; this section reports the label.

Approved uses

• X-linked hypophosphatemia in adults and children 6 months of age and older.
• Fibroblast growth factor 23-related low phosphate in tumour-induced osteomalacia, when the tumour cannot be removed or found, in adults and children 2 years of age and older.

Dosing as the label gives it for X-linked hypophosphatemia

• Before starting: the label directs that oral phosphate and active vitamin D analogs be stopped for one week, and that fasting blood phosphorus be below the reference range for age.
• Children weighing less than 10 kg: a starting dose of 1 mg/kg every two weeks.
• Children weighing 10 kg or more: a starting dose of 0.8 mg/kg, rounded to the nearest 10 mg, every two weeks, with a minimum starting dose of 10 mg and a maximum dose of 90 mg; the dose may be raised in steps up to approximately 2 mg/kg (maximum 90 mg) every two weeks to reach normal phosphorus.
• Adults: a starting dose of 1 mg/kg, rounded to the nearest 10 mg, up to 90 mg, every four weeks; if phosphorus stays low after the first 3 months, the label allows 0.5 mg/kg every two weeks and then 1 mg/kg every two weeks, not exceeding 90 mg.
• Monitoring: fasting phosphorus is checked regularly in the first 3 months, and the next dose is withheld if phosphorus runs high. The label also directs monitoring of 25-hydroxyvitamin D, with plain vitamin D (cholecalciferol or ergocalciferol) given to keep it in the normal range, while active vitamin D analogs are not given during treatment.
• The injection is given under the skin by a healthcare provider.

Contraindications

• Use together with oral phosphate and/or active vitamin D analogs, because of the risk of high blood phosphate.
• Blood phosphorus within or above the normal range for age.
• Severe kidney impairment or end-stage kidney disease.

Warnings and side effects

The label carries no boxed warning. Its warnings cover hypersensitivity reactions such as rash and hives; high blood phosphate, which may be linked to a higher risk of nephrocalcinosis; raised blood calcium, with higher risk in people with existing hyperparathyroidism, prolonged immobilisation, dehydration, excess vitamin D or kidney impairment; and injection-site reactions.

• Children (phase 3 trial, 29 on burosumab against 32 on conventional therapy): fever 55% against 19%, injection-site reaction 52% against 0%, cough 52% against 19%, vomiting 41% against 25%, tooth abscess 34% against 13% and dental caries 31% against 6%.
• Adults (24-week placebo-controlled period, 68 on burosumab against 66 on placebo): back pain 15% against 9%, headache 13% against 9%, tooth infection 13% against 9%, restless legs syndrome 12% against 8%, low vitamin D 12% against 5% and constipation 9% against 0%. High blood phosphate needing a dose reduction occurred in 7% of adults on burosumab, and was managed by halving the dose.
• Restless legs: about 12% of adults on burosumab had new or worsened restless legs syndrome of mild to moderate severity in the blinded period; these events did not lead to stopping the drug in that period (US label).

What the 2019 Clinical Practice Recommendations State

In 2019 an international group of specialists in children's kidney disease, endocrinology, orthopaedics, dentistry, neurosurgery and rheumatology, joined by representatives of two patient associations, published evidence-based clinical practice recommendations for the diagnosis and management of X-linked hypophosphatemia in Nature Reviews Nephrology. Their summary states:

• X-linked hypophosphatemia is the most common cause of inherited phosphate wasting, with complications in children (rickets, lower-limb deformities, pain, poor mineralisation of the teeth, disproportionate short stature) and in adults (hyperparathyroidism, osteomalacia, enthesopathies, osteoarthritis, pseudofractures).
• The characteristics and severity vary between patients.
• Because the condition is rare, diagnosis and specific treatment are frequently delayed, which harms outcomes.
• The panel recommends that the diagnosis rest on signs of rickets and/or osteomalacia with low blood phosphate and kidney phosphate wasting, in the absence of vitamin D or calcium deficiency.
• Whenever possible, the panel states, the diagnosis is confirmed by molecular genetic analysis or by measuring fibroblast growth factor 23 before treatment.
• Because the disease affects many systems, the panel describes regular review by multidisciplinary teams organised by a metabolic bone disease expert (Haffner 2019).

Several panel members disclosed research support or fees from the manufacturer of burosumab (Haffner 2019).

What Is Not Known

• Hearing. The 2025 review found no studies of burosumab's effect on hearing loss and states that there is currently no evidence that either conventional therapy or burosumab reduces the risk or severity of hearing impairment (Oh 2025).
• The spine. The label states that it is unknown whether burosumab worsens spinal stenosis or spinal cord compression (US label).
• Enthesopathy. None of the trial abstracts cited on this page report whether burosumab prevents or reverses the hardened tendon attachments that the French study linked to poor quality of life in adults (Herrou 2022).
• Pain and function in adults. In the blinded 24-week period, the improvements in physical function and worst pain did not reach statistical significance after correction for multiple comparisons (Insogna 2018); the later gains were measured after everyone was on the drug, without a placebo group (Briot 2021).
• Stopping treatment. The evidence that benefits fade when burosumab is interrupted comes from a post-hoc analysis of 7 people (Kamenicky 2023).
• Parathyroid glands. The 2025 meta-analysis found that tertiary hyperparathyroidism prevalence did not differ by treatment type, and notes reports of tertiary hyperparathyroidism in patients starting burosumab (Fisch 2025).
• Adult height and teeth. The children's trials ran for 64 weeks (Carpenter 2018; Imel 2019); the abstracts do not report final adult height or lifetime dental outcomes.

Key Research Papers

1. The HYP Consortium. A gene (PEX) with homologies to endopeptidases is mutated in patients with X-linked hypophosphatemic rickets. Nat Genet. 1995;11(2):130-6. PubMed PMID: 7550339
2. Carpenter TO, Imel EA, Holm IA, Jan de Beur SM, Insogna KL. A clinician's guide to X-linked hypophosphatemia. J Bone Miner Res. 2011;26(7):1381-8. PubMed PMID: 21538511
3. Shimada T, Hasegawa H, Yamazaki Y, Muto T, Hino R, Takeuchi Y, et al. FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res. 2004;19(3):429-35. PubMed PMID: 15040831
4. Morey M, Castro-Feijóo L, Barreiro J, Cabanas P, Pombo M, Gil M, et al. Genetic diagnosis of X-linked dominant Hypophosphatemic Rickets in a cohort study: tubular reabsorption of phosphate and 1,25(OH)2D serum levels are associated with PHEX mutation type. BMC Med Genet. 2011;12:116. PubMed PMID: 21902834
5. Carpenter TO, Whyte MP, Imel EA, Boot AM, Högler W, Linglart A, et al. Burosumab Therapy in Children with X-Linked Hypophosphatemia. N Engl J Med. 2018;378(21):1987-1998. PubMed PMID: 29791829
6. Imel EA, Glorieux FH, Whyte MP, Munns CF, Ward LM, Nilsson O, et al. Burosumab versus conventional therapy in children with X-linked hypophosphataemia: a randomised, active-controlled, open-label, phase 3 trial. Lancet. 2019;393(10189):2416-2427. PubMed PMID: 31104833
7. Insogna KL, Briot K, Imel EA, Kamenický P, Ruppe MD, Portale AA, et al. A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial Evaluating the Efficacy of Burosumab, an Anti-FGF23 Antibody, in Adults With X-Linked Hypophosphatemia: Week 24 Primary Analysis. J Bone Miner Res. 2018;33(8):1383-1393. PubMed PMID: 29947083
8. Briot K, Portale AA, Brandi ML, Carpenter TO, Cheong HI, Cohen-Solal M, et al. Burosumab treatment in adults with X-linked hypophosphataemia: 96-week patient-reported outcomes and ambulatory function from a randomised phase 3 trial and open-label extension. RMD Open. 2021;7(3):e001714. PubMed PMID: 34548383
9. Kamenicky P, Briot K, Brandi ML, Cohen-Solal M, Crowley RK, Keen R, et al. Benefit of burosumab in adults with X-linked hypophosphataemia (XLH) is maintained with long-term treatment. RMD Open. 2023;9(1):e002676. PubMed PMID: 36854566
10. Haffner D, Emma F, Eastwood DM, Biosse Duplan M, Bacchetta J, Schnabel D, et al. Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia. Nat Rev Nephrol. 2019;15(7):435-455. PubMed PMID: 31068690
11. Taylor A, Sherman NH, Norman ME. Nephrocalcinosis in X-linked hypophosphatemia: effect of treatment versus disease. Pediatr Nephrol. 1995;9(2):173-5. PubMed PMID: 7794712
12. DeLacey S, Liu Z, Broyles A, El-Azab SA, Guandique CF, James BC, et al. Hyperparathyroidism and parathyroidectomy in X-linked hypophosphatemia patients. Bone. 2019;127:386-392. PubMed PMID: 31276850
13. Lecoq AL, Chaumet-Riffaud P, Blanchard A, Dupeux M, Rothenbuhler A, Lambert B, et al. Hyperparathyroidism in Patients With X-Linked Hypophosphatemia. J Bone Miner Res. 2020;35(7):1263-1273. PubMed PMID: 32101626
14. Fisch SA, Zilberman S, Tudor A, Benchekroun EM, Landsberg W, Rundle AG, et al. Secondary and Tertiary Hyperparathyroidism among Patients with X-Linked Hypophosphatemia: A Systematic Review and Meta-analysis. Calcif Tissue Int. 2025;117(1):4. PubMed PMID: 41437161
15. Sandy JL, Nunez C, Wheeler BJ, Jefferies C, Morris A, Siafarikas A, et al. Prevalence and characteristics of paediatric X-linked hypophosphataemia in Australia and New Zealand: Results from the Australian and the New Zealand Paediatric Surveillance Units survey. Bone. 2023;173:116791. PubMed PMID: 37263386
16. Baroncelli GI, Zampollo E, Manca M, Toschi B, Bertelloni S, Michelucci A, et al. Pulp chamber features, prevalence of abscesses, disease severity, and PHEX mutation in X-linked hypophosphatemic rickets. J Bone Miner Metab. 2021;39(2):212-223. PubMed PMID: 32772199
17. Herrou J, Picaud AS, Lassalle L, Pacot L, Chaussain C, Merzoug V, et al. Prevalence of Enthesopathies in Adults With X-linked Hypophosphatemia: Analysis of Risk Factors. J Clin Endocrinol Metab. 2022;107(1):e224-e235. PubMed PMID: 34406383
18. Oh S, Sandy JL, Munns CF, Simm PJ, Siafarikas A, Collins L, et al. Hearing impairment in X-linked hypophosphatemia: a review. JBMR Plus. 2025;9(Suppl 5):v14-v29. PubMed PMID: 41445554
19. Seefried L, Smyth M, Keen R, Harvengt P. Burden of disease associated with X-linked hypophosphataemia in adults: a systematic literature review. Osteoporos Int. 2021;32(1):7-22. PubMed PMID: 32710160
20. Hawley S, Shaw NJ, Delmestri A, Prieto-Alhambra D, Cooper C, Pinedo-Villanueva R, et al. Higher prevalence of non-skeletal comorbidity related to X-linked hypophosphataemia: a UK parallel cohort study using CPRD. Rheumatology (Oxford). 2021;60(9):4055-4062. PubMed PMID: 33331900
21. Munns CF, Shaw N, Kiely M, Specker BL, Thacher TD, Ozono K, et al. Global Consensus Recommendations on Prevention and Management of Nutritional Rickets. J Clin Endocrinol Metab. 2016;101(2):394-415. PubMed PMID: 26745253
22. US label: burosumab injection, for subcutaneous use (DailyMed set ID 102f96a0-6e3a-4fc1-b204-34d604683af6, version 7, published July 2026). DailyMed label

PubMed Topic Searches

1. PubMed: X-linked hypophosphatemia
2. PubMed: Burosumab trials in X-linked hypophosphatemia
3. PubMed: PHEX, fibroblast growth factor 23 and phosphate wasting
4. PubMed: Enthesopathy in X-linked hypophosphatemia
5. PubMed: Nephrocalcinosis and hyperparathyroidism in X-linked hypophosphatemia

Connections

• Endocrinology — the parent section for hormone disorders
• Phosphorus — the mineral this condition drains
• Phosphorus for Bone Mineralization — how phosphate hardens bone and the hormone axis that controls it
• Hypophosphatemia: Bone Pain and Softening — low phosphate from every cause
• Vitamin D Deficiency: Rickets in Children — the nutritional form of rickets
• Vitamin D Deficiency: Bone Pain and Osteomalacia — soft bone in adults from a lack of vitamin D
• Intravenous Iron and Low Phosphate — the same hormone raised by a medicine
• Secondary Hyperparathyroidism — the parathyroid complication in more depth

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