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Osteomalacia and Rickets

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Osteomalacia and Rickets

BASICS

DESCRIPTION

Heritable disorders of rickets include (2): ‚

Perform a complete physical and dental examination in children. ‚

Initial Tests (lab, imaging)

Bone biopsy is not usually done in adults because the diagnosis can be made from the history, physical exam, and a combination of laboratory and radiologic studies; however, the most accurate diagnosis is made by bone biopsy using double tetracycline labeling. ‚

Surgery may be necessary to repair severe bone abnormalities. ‚

11 Pettifor ‚ JM. Nutritional rickets: pathogenesis and prevention. Pediatr Endocrinol Rev. 2013;10(Suppl 2):347 " “353.22 Holick ‚ MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266 " “281.33 Wagner ‚ CL, Greer ‚ FR. Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics. 2008;122(5):1142 " “1152.44 Ross ‚ AC, Manson ‚ JE, Abrams ‚ SA, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96(1):53 " “58.55 Elder ‚ CJ, Bishop ‚ NJ. Rickets. Lancet. 2014;383(9929):1665 " “1676.66 Pramyothin ‚ P, Holick ‚ MF. Vitamin D supplementation: guidelines and evidence for subclinical deficiency. Curr Opin Gastroenterol. 2012;28(2):139 " “150.

  • A metabolic bone disorder due to decreased bone mineralization (calcification) and increased organic bone matrix that results in decreased bone density
  • Referred to as renal osteodystrophy when secondary to renal disease
  • System(s) affected: musculoskeletal

EPIDEMIOLOGY

  • ChildrenMedian age of presentation is 15 months.Infants develop vitamin D " “deficiency rickets (1).Adolescents develop nutritional rickets due to calcium deficiency (1).
  • Adults: elderly, rare and increasing
  • Median age of presentation is 15 months.
  • Infants develop vitamin D " “deficiency rickets (1).
  • Adolescents develop nutritional rickets due to calcium deficiency (1).

ETIOLOGY AND PATHOPHYSIOLOGY

  • Abnormalities of mineralization ossification or interference caused by insufficient circulating levels of calcium, phosphate, or vitamin D
  • Children: Rickets is a disease of the physes (growth plates) characterized not only by deficient mineralization of cartilage and osteoid but also by retarded endochondral ossification, which causes excessive accumulation of physeal cartilage, growth failure, and skeletal deformities.
  • Adults: disorder of mineralization of newly formed bone matrix
  • Impaired intestinal absorption of calcium/phosphorus due to celiac disease, cystic fibrosis, or postgastrectomy
  • Hypophosphatemia from secondary hyperparathyroidism due to vitamin D deficiency is the primary cause in adults.
  • Vitamin D " “metabolism abnormalities, including hepatic or renal disease
  • Resistance to vitamin D
  • Impaired renal phosphate absorption associated with proximal or distal renal tubular defects
  • Causes that inhibit mineralization of the growth plate and osteoidAlkaline phosphatase deficiencyAluminum toxicityFluoride toxicityPrimary hyperparathyroidism
  • Drugs that may affect absorption or metabolism of calcium, phosphorus, or vitamin DAntacidsAntiepileptic drugsCorticosteroidsLoop diuretics
  • Drugs that inhibit mineralization: bisphosphonates
  • Oncogenic osteomalacia
  • Sickle cell
  • Alkaline phosphatase deficiency
  • Aluminum toxicity
  • Fluoride toxicity
  • Primary hyperparathyroidism
  • Antacids
  • Antiepileptic drugs
  • Corticosteroids
  • Loop diuretics
  • Vitamin D " “dependent rickets type 1 " ”causes reduced or no renal synthesis of 1,25-dihydroxyvitamin D (calcitriol)
  • Vitamin D " “dependent rickets type 2 " ”causes partial or complex resistance to calcitriol, resulting in elevated levels of calcitriol
  • Vitamin D " “dependent rickets type 3 " ”prevents the action of calcitriol in transcription causing resistance and elevated levels calcitriol
  • Autosomal dominant hypophosphatemic rickets " ”causes phosphaturia, decreased intestinal absorption of phosphorus, and decreased 25-hydroxyvitamin D (calcidiol), resulting in low calcitriol
  • X-linked hypophosphatemic rickets " ”causes phosphaturia, decreased intestinal absorption of phosphorus, decreased calcidiol, resulting in low calcitriol

RISK FACTORS

  • Eating disorder
  • Increased melanin skin pigmentation
  • Malabsorption
  • Vegetarian diet without vitamin supplementation
  • Limited sunlight exposure (high latitude, overcrowding, religious customs limiting adequate skin exposure to UV irradiation, working indoors)
  • Poverty
  • ChildrenBreastfeeding as a sole source of nutrition without vitamin D supplementationBreastfed infants born to mothers who themselves are vitamin D deficientPrematurity
  • AdultsPoor diet low in calcium and high in phytatePrimary biliary cirrhosisRenal failureGastrectomy
  • Breastfeeding as a sole source of nutrition without vitamin D supplementation
  • Breastfed infants born to mothers who themselves are vitamin D deficient
  • Prematurity
  • Poor diet low in calcium and high in phytate
  • Primary biliary cirrhosis
  • Renal failure
  • Gastrectomy

GENERAL PREVENTION

  • Adequate vitamin D intake: Encourage foods, such as fatty fish, cod liver oil, egg yolks, and fortified foods (3)[C].
  • ChildrenAmerican Academy of Pediatrics recommends a minimum vitamin D intake of 400 IU/day starting within the first few days of life.Infants who consume >1 L/day of vitamin D " “fortified formula or whole milk will receive the recommended vitamin D intake.Supplementation is recommended for breastfed infants and children consuming <1 L/day of vitamin D " “fortified formula or milk.
  • Adults70 years old and younger, vitamin D, 600 IU/day (4)[A]71 years and older, vitamin D, 800 IU/day (4)[A]
  • Adequate calcium intake:4 years old or older, calcium, over 1,000 mg/day (4)[A]If calcium-rich foods are unavailable, then powdered limestone, calcium-rich vegetables, and/or ground bony fish powder (1)[C]
  • Pregnancy (4)[A]Ergocalciferol 600 IU/day for routine pregnancyErgocalciferol 1,000 to 2,000 IU/day is safe if vitamin D deficient.
  • American Academy of Pediatrics recommends a minimum vitamin D intake of 400 IU/day starting within the first few days of life.
  • Infants who consume >1 L/day of vitamin D " “fortified formula or whole milk will receive the recommended vitamin D intake.
  • Supplementation is recommended for breastfed infants and children consuming <1 L/day of vitamin D " “fortified formula or milk.
  • 70 years old and younger, vitamin D, 600 IU/day (4)[A]
  • 71 years and older, vitamin D, 800 IU/day (4)[A]
  • 4 years old or older, calcium, over 1,000 mg/day (4)[A]
  • If calcium-rich foods are unavailable, then powdered limestone, calcium-rich vegetables, and/or ground bony fish powder (1)[C]
  • Ergocalciferol 600 IU/day for routine pregnancy
  • Ergocalciferol 1,000 to 2,000 IU/day is safe if vitamin D deficient.

COMMONLY ASSOCIATED CONDITIONS

  • Children with vitamin D " “deficiency ricketsSecondary hyperparathyroidismDilated cardiomyopathyMarrow fibrosis with pancytopenia or microcytic hypochromic anemiaDysregulation of immune function and cellular differentiation and proliferation
  • Adults with osteomalaciaChronic renal diseaseGastrectomyEpilepsyMalnutrition
  • Secondary hyperparathyroidism
  • Dilated cardiomyopathy
  • Marrow fibrosis with pancytopenia or microcytic hypochromic anemia
  • Dysregulation of immune function and cellular differentiation and proliferation
  • Chronic renal disease
  • Gastrectomy
  • Epilepsy
  • Malnutrition

DIAGNOSIS

HISTORY

  • Signs and symptoms of hypocalcemiaMuscle crampsNumbnessParesthesiasTetanySeizuresDiarrhea
  • Common presentations in children (3)Muscle weakness: may not be able to stand until age 3 yearsBowed legsDiffuse limb painHypocalcemic seizuresCarpopedal spasms
  • Common presentations in adultsDull bony pain and tenderness typically in lower spine and pelvis that is aggravated by activity and weight bearingMuscle weakness, especially the proximal lower extremityFractures may occur with little or no trauma.
  • Muscle cramps
  • Numbness
  • Paresthesias
  • Tetany
  • Seizures
  • Diarrhea
  • Muscle weakness: may not be able to stand until age 3 years
  • Bowed legs
  • Diffuse limb pain
  • Hypocalcemic seizures
  • Carpopedal spasms
  • Dull bony pain and tenderness typically in lower spine and pelvis that is aggravated by activity and weight bearing
  • Muscle weakness, especially the proximal lower extremity
  • Fractures may occur with little or no trauma.

PHYSICAL EXAM

  • GeneralPalpate entire skeletal system to search for tenderness and bony abnormalities.Evaluate for growth abnormalities such as decreased height and spinal deformity.
  • Head, ears, eyes, nose, and throatCraniotabes (thinning and softening of occipital and parietal bones)Late closing of fontanellesFontal bossing of skullDelayed dentition
  • ChestRachitic rosary (enlarged costochondral joints felt lateral to nipple line)Harrison groove (flaring of ribs at diaphragm level)Pigeon chest (protrusion of the sternum)
  • BackLordosis/kyphosisScoliosis
  • ExtremitiesBowing or widening of the physisGenu valgum (knock knee)Flaring of the wristsFraying and cupping of metaphysisGenu varum (bowed knees)
  • NeurologicGait disturbances in an ambulatory childSigns of hypocalcemiaHyperreflexiaNeuromuscular instability: Chvostek sign (tap cranial nerve VII), Trousseau sign (carpopedal spasm 2 to 3 minutes after BP cuff is inflated proximally)Tetany, myopathy, seizures, spasm, muscle weakness
  • In adultsProximal muscle weakness, possible muscle wasting, hypotonia, and discomfort with movementWaddling gaitBone pain and tenderness to palpation: most pronounced in the lower spine, pelvis, and lower extremities
  • Palpate entire skeletal system to search for tenderness and bony abnormalities.
  • Evaluate for growth abnormalities such as decreased height and spinal deformity.
  • Craniotabes (thinning and softening of occipital and parietal bones)
  • Late closing of fontanelles
  • Fontal bossing of skull
  • Delayed dentition
  • Rachitic rosary (enlarged costochondral joints felt lateral to nipple line)
  • Harrison groove (flaring of ribs at diaphragm level)
  • Pigeon chest (protrusion of the sternum)
  • Lordosis/kyphosis
  • Scoliosis
  • Bowing or widening of the physis
  • Genu valgum (knock knee)
  • Flaring of the wrists
  • Fraying and cupping of metaphysis
  • Genu varum (bowed knees)
  • Gait disturbances in an ambulatory child
  • Signs of hypocalcemia
  • Hyperreflexia
  • Neuromuscular instability: Chvostek sign (tap cranial nerve VII), Trousseau sign (carpopedal spasm 2 to 3 minutes after BP cuff is inflated proximally)
  • Tetany, myopathy, seizures, spasm, muscle weakness
  • Proximal muscle weakness, possible muscle wasting, hypotonia, and discomfort with movement
  • Waddling gait
  • Bone pain and tenderness to palpation: most pronounced in the lower spine, pelvis, and lower extremities

DIFFERENTIAL DIAGNOSIS

  • ChildrenLiver diseaseFailure to thriveDevelopmental delayOrthopedic abnormalitiesCongenital syphilisChild abuseAlkaline phosphatase deficiencyToxicity (aluminum, fluoride)Primary hyperparathyroidism (rare)
  • AdultsOsteoporosisHyperparathyroidismMetastatic bone diseaseLymphoma/myelomaFibromyalgia
  • Liver disease
  • Failure to thrive
  • Developmental delay
  • Orthopedic abnormalities
  • Congenital syphilis
  • Child abuse
  • Alkaline phosphatase deficiency
  • Toxicity (aluminum, fluoride)
  • Primary hyperparathyroidism (rare)
  • Osteoporosis
  • Hyperparathyroidism
  • Metastatic bone disease
  • Lymphoma/myeloma
  • Fibromyalgia

DIAGNOSTIC TESTS & INTERPRETATION

  • Vitamin D deficiency (5)[A]Serum phosphorus: decreasedPlasma calcium: decreased/normalSerum calcidiol: decreasedAlkaline phosphatase: increasedParathyroid hormone: increased
  • Renal phosphate-wasting osteomalaciaSerum phosphorous: decreasedPhosphate clearance: increasedSerum calcium: normalAlkaline phosphatase: normalParathyroid hormone: normal
  • Serum phosphorus: decreased
  • Plasma calcium: decreased/normal
  • Serum calcidiol: decreased
  • Alkaline phosphatase: increased
  • Parathyroid hormone: increased
  • Serum phosphorous: decreased
  • Phosphate clearance: increased
  • Serum calcium: normal
  • Alkaline phosphatase: normal
  • Parathyroid hormone: normal
  • Blood testsSerum calcium (total and ionized), phosphate, BUN, creatinine, electrolytesSerum calcidiol, deficiency <20 ng/mL, insufficiency 20 to 29 ng/mLAlkaline phosphataseParathyroid hormone
  • UrinalysisCalcium, phosphate, creatinine in spot urine sample
  • Radiographic imaging: anteroposterior images of rapidly growing skeletal areas: Knees, wrists, and anterior ends may show Looser transformation zones.
  • Children: radiographic changes in rapidly growing skeletal areas (knee, wrist), including widening of the distal epiphysis, fraying and widening of the metaphysis, and angular deformities of the arm and leg bones (3,4)Widening of distal physisFraying and widening of the metaphysisAngular deformities of arm and leg bones
  • AdultsReduced bone density with thinning of the cortexChanges in vertebral bodies: loss of radiologic distinctness and concavity of the vertebral bodyCharacteristic finding: Looser zones:Pseudofractures, fissures, or narrow radiolucent lines, 2 to 5 mm in width with sclerotic bordersUsually located at the femoral neck, on the medial part of the femoral shaft, immediately under the lesser trochanter, or a few centimeters beneath the pubic and ischial rami
  • Serum calcium (total and ionized), phosphate, BUN, creatinine, electrolytes
  • Serum calcidiol, deficiency <20 ng/mL, insufficiency 20 to 29 ng/mL
  • Alkaline phosphatase
  • Parathyroid hormone
  • Calcium, phosphate, creatinine in spot urine sample
  • Widening of distal physis
  • Fraying and widening of the metaphysis
  • Angular deformities of arm and leg bones
  • Reduced bone density with thinning of the cortex
  • Changes in vertebral bodies: loss of radiologic distinctness and concavity of the vertebral body
  • Characteristic finding: Looser zones:Pseudofractures, fissures, or narrow radiolucent lines, 2 to 5 mm in width with sclerotic bordersUsually located at the femoral neck, on the medial part of the femoral shaft, immediately under the lesser trochanter, or a few centimeters beneath the pubic and ischial rami
  • Pseudofractures, fissures, or narrow radiolucent lines, 2 to 5 mm in width with sclerotic borders
  • Usually located at the femoral neck, on the medial part of the femoral shaft, immediately under the lesser trochanter, or a few centimeters beneath the pubic and ischial rami

TREATMENT

MEDICATION

  • Calcium 1,000 mg/day PO
  • Children with vitamin D " “deficiency rickets (6)[A]Infants, ergocalciferol 2,000 IU/day or 50,000 IU/week for 6 weeks, maintenance ergocalciferol 400 to 1,000 IU/dayChildren, ergocalciferol 2,000 IU/day or 50,000 IU/week for 6 weeks, maintenance ergocalciferol 600 to 1,000 IU/dayTreat to serum calcidiol 30 ng/mL, then proceed with maintenance dose.
  • Adults with vitamin D " “deficiency osteomalaciaErgocalciferol 50,000 IU/week for 8 weeks, treat to serum calcidiol 30 ng/mL, then proceed with maintenance dose of 1,500 to 2,000 IU/day
  • MalabsorptionErgocalciferol 6,000 to 10,000 IU/day, treat to serum calcidiol of 30 ng/mL, then proceed with maintenance dose of 3,000 to 6,000 IU/dayUp to 4 g/day of calcium
  • Infants, ergocalciferol 2,000 IU/day or 50,000 IU/week for 6 weeks, maintenance ergocalciferol 400 to 1,000 IU/day
  • Children, ergocalciferol 2,000 IU/day or 50,000 IU/week for 6 weeks, maintenance ergocalciferol 600 to 1,000 IU/day
  • Treat to serum calcidiol 30 ng/mL, then proceed with maintenance dose.
  • Ergocalciferol 50,000 IU/week for 8 weeks, treat to serum calcidiol 30 ng/mL, then proceed with maintenance dose of 1,500 to 2,000 IU/day
  • Ergocalciferol 6,000 to 10,000 IU/day, treat to serum calcidiol of 30 ng/mL, then proceed with maintenance dose of 3,000 to 6,000 IU/day
  • Up to 4 g/day of calcium

ADDITIONAL THERAPIES

SURGERY/OTHER PROCEDURES

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

  • For children, monitor the following:Serum calcium, phosphorus, alkaline phosphatase, calcidiolSerum phosphorus should increase during the 1st week of treatment, followed by an increase in serum calcium.Urinary calcium and phosphorus levels, spot urine calcium (should be increasing)
  • For adults taking calcium supplements, monitor the following:Plasma and urinary levels of calcium
  • Serum calcium, phosphorus, alkaline phosphatase, calcidiolSerum phosphorus should increase during the 1st week of treatment, followed by an increase in serum calcium.
  • Urinary calcium and phosphorus levels, spot urine calcium (should be increasing)
  • Serum phosphorus should increase during the 1st week of treatment, followed by an increase in serum calcium.
  • Plasma and urinary levels of calcium

PROGNOSIS

  • Varies depending on the etiology
  • Vitamin D " “causes of ricketsRadiographic evidence of healing occur within 2 to 3 months and lags behind clinical and biochemical improvement by a few weeks.
  • Radiographic evidence of healing occur within 2 to 3 months and lags behind clinical and biochemical improvement by a few weeks.

COMPLICATIONS

  • Fractures: ribs, vertebrae, and long bones
  • Osteomyelitis
  • Renal failure
  • Renal tubular acidosis
  • Hypocalcemic seizures/muscle spasms
  • Growth deformity and bowing of the long bones in children

REFERENCES

ADDITIONAL READING

  • American College of Obstetricians Committee on Obstetric Practice. ACOG Committee Opinion No. 495: vitamin D: screening and supplementation during pregnancy. Obstet Gynecol. 2011;118(1):197 " “198.
  • Christodoulou ‚ S, Goula ‚ T, Ververidis ‚ A, et al. Vitamin D and bone disease. Biomed Res Int. 2013;2013:396541.
  • Misra ‚ M, Pacaud ‚ D, Petryk ‚ A, et al. Vitamin D deficiency in children and its management: review of current knowledge and recommendations. Pediatrics. 2008;122(2):398 " “417.
  • Shore ‚ RM, Chesney ‚ RW. Rickets: part I. Pediatr Radiol. 2013;43(2):140 " “151.
  • Shore ‚ RM, Chesney ‚ RW. Rickets: part II. Pediatr Radiol. 2013;43(2):152 " “172.

CODES

ICD10

  • M83.9 Adult osteomalacia, unspecified
  • E55.0 Rickets, active
  • N25.0 Renal osteodystrophy
  • M83.1 Senile osteomalacia
  • M83.5 Other drug-induced osteomalacia in adults
  • M83.4 Aluminum bone disease
  • M83.3 Adult osteomalacia due to malnutrition
  • M83.2 Adult osteomalacia due to malabsorption
  • M83.8 Other adult osteomalacia

ICD9

  • 268.2 Osteomalacia, unspecified
  • 268.0 Rickets, active
  • 275.3 Disorders of phosphorus metabolism

SNOMED

  • Osteomalacia (disorder)
  • Rickets (disorder)
  • Senile osteomalacia (disorder)
  • Adult osteomalacia due to malabsorption
  • adult osteomalacia due to malnutrition (disorder)
  • Aluminum-related osteomalacia (disorder)
  • Osteomalacia secondary to drug (disorder)

CLINICAL PEARLS

  • In the United States, rickets occurs almost exclusively in breastfed infants without vitamin D supplementation or sun exposure.
  • Children and adolescents with increased skin pigmentation, decreased sun exposure, cystic fibrosis, or taking anticonvulsants may require higher doses than 400 IU/day (3).
  • Suspect osteomalacia in adults with bone pain.