eMedicine Specialties > Pediatrics: General Medicine > Endocrinology
Hypophosphatemic Rickets: Treatment & Medication
Updated: Feb 6, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
- Treatment of hypophosphatemic rickets can be safely administered on an outpatient basis, although serum calcium concentrations must be periodically and carefully monitored. Conscientious follow-up is essential.
- The usual vitamin D preparations are not useful for treatment in this disorder because they lack significant 1-alpha-hydroxylase activity. Original treatment protocols advocated vitamin D at levels of 25,000-50,000 U/d (at the lower limit of toxic dosage), which placed the patient in jeopardy of frequent hypercalcemic episodes. Calcitriol is now more widely available and substantially diminishes, but does not eliminate, this risk. Amiloride and hydrochlorothiazide are administered to enhance calcium reabsorption and to reduce the risk of nephrocalcinosis.
Surgical Care
- Osteotomy to realign extremely distorted leg curvatures may be necessary for children whose diagnosis was delayed or whose initial treatment was inadequate. Skull deformity may require treatment for synostosis.
- Spontaneous abscesses often require periodic dental procedures.
Consultations
- Consult a nephrologist for help treating any patient with possible kidney involvement.
Activity
- If a patient is able, no activity restrictions are needed. Affected individuals obviously should not engage in contact sports until rickets is completely healed.
Medication
Treatment options include calcitriol, growth hormone, phosphates, and anticalciurics to promote healthy bone growth and diminish mineral loss associated with hypophosphatemic rickets.
Vitamin D
Standard protocol for treatment of familial hypophosphatemic rickets includes the use of 1,25-dihydroxy-vitamin D (calcitriol). Use of calcitriol in place of standard vitamin D obviates near-toxic dosage of the latter, avoids fat storage of parent vitamin D, and diminishes the danger of hypercalcemia.
Calcitriol (Rocaltrol)
Increases Ca levels by promoting Ca absorption in intestines and retention in kidneys.
Adult
50 ng/kg/d PO initially; make no change in initial dose for at least 4 wk; increases should be made in 5 ng/kg/d increments; not to exceed 65-70 ng/kg/d
Pediatric
Administer as in adults
Cholestyramine and colestipol decrease absorption of calcitriol; magnesium-containing antacids and thiazide diuretics can increase calcitriol effects
Documented hypersensitivity; hypercalcemia, malabsorption syndrome
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Symptoms of hypercalcemia include weakness, nausea, myalgia, constipation; adequate response to calcitriol depends on adequate dietary Ca intake; maintain adequate fluid intake; caution in breastfeeding women
Growth Hormone
These agents enhance growth in affected children.
Somatropin (Genotropin, Humatrope)
Human growth hormone is commercially produced from the human gene implanted into the DNA of Escherichia coli. It is currently in widespread use for treatment of growth failure from many etiologies by enhancement of growth velocity.
Adult
0.05-0.1 mg/kg/wk SC
Pediatric
0.18-0.375 mg/kg/wk SC in 6-7 divided doses
Glucocorticoids may diminish the growth-related effect
Documented hypersensitivity; closed epiphyses; actively growing intracranial tumor; any underlying intracranial lesion
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in diabetes
Phosphate replacement
Massive urinary phosphate loss is a problem intrinsic to the disorder, and the phosphate must be replaced.
Phosphate salts (Neutra-Phos-K)
Neutralized, buffered PO phosphate replacement solution, containing 1000 mg of P (32 μmol inorganic phosphate) per 300 mL or 4 cap or packets. Combination of NA and K phosphate.
Adult
1-3 g/d elemental P (ie, 4-12 capsules or packets/d); mix each cap or packet with 75 mL of water
Pediatric
10 mg/kg/d phosphate PO; increases should be made to maintain serum phosphate concentration >4.5 mg/dL (infants) and 2 mg/dL (children); mix each cap or packet with 75 mL of water
Mg-containing and Al-containing antacids or sucralfate can act as phosphate binders and decrease serum phosphate levels; K-sparing diuretics, ACE inhibitors, and salt substitutes may increase serum phosphate levels; in the presence of hypercalcemia, PO phosphate solutions create generalized calcinosis, with particular reference to renal parenchyma
Documented hypersensitivity; hyperphosphatemia; hypocalcemia; hypomagnesemia; hyperkalemia; renal failure
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in patients with renal insufficiency and metabolic alkalosis; admixture of phosphate and Ca in IV fluids can result in Ca phosphate precipitation; close monitoring of serum Ca and phosphate concentrations is essential; additional caution is required with TPN; GI adverse effects including diarrhea, nausea, stomach pain, and flatulence may occur; take with food to minimize risk of diarrhea; mix in 6-8 oz of water prior to administration
Diuretics
Thiazides are anticalciuric, an effect that can assist in counteracting the tendency for bone Ca loss.
Hydrochlorothiazide (Esidrix, HydroDIURIL)
Well-known diuretic with antihypertensive action. Inhibits reabsorption of Na in distal tubules, causing increased excretion of Na and water as well as K and H ions. Not metabolized and is rapidly excreted in the urine
Adult
25 mg PO qd initial; not to exceed 100 mg/d
Pediatric
<6 months: Doses as high as 3 mg/k/d PO may be necessary
6 months to 2 years: 1-2 mg/kg/d PO; not to exceed 38 mg/d
>2 years: 1-2 mg/kg/d PO; not to exceed 100 mg/d
Thiazides may decrease effects of anticoagulants, antigout agents, sulfonylureas; thiazides may increase toxicity of allopurinol, anesthetics, antineoplastics, Ca salts, loop diuretics, lithium, diazoxide, digitalis, amphotericin B, nondepolarizing muscle relaxants
Documented hypersensitivity; anuria or renal decompensation
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in renal disease, hepatic disease, gout, diabetes mellitus, and erythematosus; electrolyte depletion is natural result of thiazide usage and must be avoided by close serum electrolyte monitoring, especially in hot weather; hypokalemia a paramount concern, and K supplementation advisable
Amiloride (Midamor)
Kaliuretic-effect thiazides create hazard of hypokalemia, a danger that can be counteracted by use of a second diuretic. Amiloride has a well-characterized antikaliuretic effect. Often used together with thiazides for its synergistic antihypertensive effects, has benefit of decreasing K loss. Thus, it is a useful adjunct in the treatment of patients with familial x-linked hypophosphatemia with thiazides, in whom hypokalemia is a risk.
Adult
5 mg PO qd as adjunctive therapy; not to exceed 20 mg/d
Pediatric
0.2 mg/kg PO; not to exceed 5 mg/d
Concomitant therapy with ACE inhibitors, cyclosporine, or K supplementation may increase serum K levels, if concomitant use of these agents indicated because of demonstrated hypokalemia, caution and monitor serum K frequently; Li generally should not be given with diuretics because may reduce renal clearance and add high risk of Li toxicity; NSAIDs reduce diuretic, natriuretic, and antihypertensive effects of diuretics, observe patient closely to determine if desired effect of diuretic obtained; indomethacin and K-sparing diuretics, including amiloride, may be associated with increased serum L levels, consider potential effects on K kinetics and renal function
Documented hypersensitivity; elevated serum potassium levels >5.5 mEq/L; impaired renal function, acute or chronic renal insufficiency, evidence of diabetic nephropathy; monitor electrolytes closely if evidence suggests renal functional impairment, BUN level >30 mg per 100 mL or serum creatinine levels >1.5 mg per 100 mL
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
K retention associated with use of an antikaliuretic agent accentuated in presence of renal impairment and may result in rapid development of hyperkalemia; monitor serum K level, mild hyperkalemia usually not associated with abnormal ECG findings; adverse effects include GI upset, dry mouth, skin rash, confusion, postural hypotension, hyperkalemia, hyponatremia; caution in severe hepatic insufficiency; take with food or milk
More on Hypophosphatemic Rickets |
| Overview: Hypophosphatemic Rickets |
| Differential Diagnoses & Workup: Hypophosphatemic Rickets |
 Treatment & Medication: Hypophosphatemic Rickets |
| Follow-up: Hypophosphatemic Rickets |
| References |
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References
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Further Reading
Keywords
hypophosphatemic rickets, familial hypophosphatemic rickets, vitamin D-resistant rickets, X-linked hypophosphatemic rickets, X-linked hypophosphatemic osteomalacia, rachitic disease, vitamin D ingestion, vitamin D–resistant rickets, hypophosphatemia, proteolysis, hyperphosphaturia, short stature, dental abscess, delayed dentition, bone deformation, cranial synostosis, short stature
