Bone mineral disorders

19.5 Bone mineral disorders



Colin Jones, Joshua Kausman


Hypocalcaemia, rickets and hypercalcaemia are the most common manifestations of disorders of calcium, phosphate and vitamin D metabolism. Disorders of magnesium metabolism are rare but share many features of calcium disorders.



Calcium, magnesium and phosphorus (Table 19.5.1)


Calcium and phosphate form the major structural components of bone, in the form of hydroxyapatite. The majority of magnesium is also found in bones. A large proportion of each mineral in bone is freely exchangeable with the extracellular fluid (ECF). Calcium and phosphate ions, under normal circumstances, are present in supersaturated solution. A rise in phosphate will lead to the deposition of more calcium phosphate into bone as hydroxyapatite and cause hypocalcaemia. The distribution of calcium and phosphate between bone and the ECF is determined by hormonal regulation of the concentrations of these minerals. The most important hormones are 1,25-dihydroxyvitamin D3 (activated vitamin D) and parathyroid hormone (PTH). The actions of these hormones are summarized in Figure 19.5.1.



Table 19.5.1 Distribution, serum concentrations, dietary requirements and sources of calcium, magnesium and phosphate

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Fig. 19.5.1 Hormonal control of calcium, magnesium and phosphate. PTH, parathyroid hormone.


The ionized ECF forms of calcium and magnesium are responsible for physiological effect. The ionized form of calcium should be measured to confirm that abnormalities in concentration are present, because the equilibrium between the ionized and protein-bound forms can change. For instance, an increase of 0.1 pH unit decreases the ionized calcium by 10%, and hypoalbuminaemia reduces total serum calcium but not the ionized calcium concentration, because 90% of bound calcium is bound to albumin.



image Clinical example


Kylie, a 6-year-old girl, has nephritis with a metabolic acidosis (pH 7.32, [HCO3−] = 15 mmol/L, Pco2 30 mmHg). She has an albumin of 20 g/L, serum total [Ca2+] = 1.0 mmol/L and serum [phosphate] = 3.6 mmol/L. Is it safe to correct the acidosis with intravenous NaHCO3? From Table 19.5.1, if the serum albumin was normal, 46% of the total serum Ca2+ would be ionized. However, the serum albumin concentration is reduced by 50%, thus the amount of calcium bound to albumin will be reduced by 50% (the proportion of total calcium bound to albumin will be reduced to approximately 20%), leaving the ionized proportion of total serum calcium increased from the normal 46% to approximately 66% = 0.66 mmol/L. Increasing the pH to 7.4 could reduce the ionized portion and precipitate overt symptoms of hypocalcaemia. Thus, the calcium concentration should be corrected before giving NaHCO3.



Hypocalcaemia


In the neonatal period, hypocalcaemia is conventionally a total serum calcium concentration below 1.8 mmol/L (ionized calcium 1.0 mmol/L). Beyond this age, a total plasma calcium below 2.1 mmol/L (ionized calcium 1.2 mmol/L) constitutes hypocalcaemia. Clinical signs usually occur only with total serum calcium below 2 mmol/L (ionized calcium 0.75 mmol/L), although some patients can tolerate much lower levels and remain asymptomatic. The signs of hypocalcaemia are due to neuromuscular excitability. Jitteriness, apnoea, laryngeal spasm causing stridor and convulsions are frequent in infants. Tetany, carpopedal spasm and the Chovstek (facial twitch on percussion of the facial nerve near the temporomandibular joint) and Trousseau (tetany produced by inflating the sphygmomanometer with above systolic blood pressure for up to 2 min) signs are seen mainly in older children. Intracerebral calcification and cataracts are complications. The electrocardiogram (ECG) may show a prolonged QT interval.


Some causes of hypocalcaemia are listed in Box 19.5.1.



Box 19.5.1 Causes of hypocalcaemia




Neonatal


• Early neonatal – prematurity, IDM, IUGR, birth asphyxia

• Late neonatal – DiGeorge syndrome, phosphate load, low magnesium, IDM

Pseudohypocalcaemia


• Hypoalbuminaemia

Vitamin D deficiency


• Nutritional deficiency

• Disorders of vitamin D metabolism

• 1α-hydroxylase deficiency

• vitamin D-dependent rickets

Parathyroid hormone-associated


• Hypoparathyroidism

• idiopathic

• autoimmune polyglandular disease (with mucocutaneous candidiasis, or Addison disease)

• calcium-sensing receptor activating mutations or antibodies

• hypomagnesaemia

• destructive lesions of the glands

• hypoplasia

• PTH receptor defect – pseudohypoparathyroidism

• Hyperphosphataemia

• tumour lysis

• renal failure

Pancreatitis


Medical treatment


• Large blood transfusion/exchange transfusion

IDM, infant of diabetic mother; IUGR, intrauterine growth retardation; PTH, parathyroid hormone.


Early neonatal hypocalcaemia is common in premature infants and infants of diabetic mothers. In premature infants, it is possibly an exaggerated response to the normal interruption of the maternofetal calcium transfer; the serum calcium falls following delivery to a nadir, reached at a few days of age, and then increases to normal levels at 1–2 weeks of age. Signs are seen within hours of birth, become most severe about 48 hours after birth and then improve spontaneously. Hypocalcaemia can be aggravated by early phosphate-rich formula feeding or hypoxic–ischaemic injury. Treatment of symptomatic infants involves intravenous (IV) calcium administration and commencement of diet, following the guidelines in Box 19.5.2.



Box 19.5.2 Treatment of hypocalcaemia



Emergency




• Patients with hypocalcaemia and symptoms should be treated with intravenous calcium*


• ECG monitor (bradycardia)


• IV calcium chloride 10% 0.2 mL per kg per dose (max 1 g) repeated 4–6-hourly or followed by infusion 1 mmol (= 1.5 mL 10% CaCl2) per kg per day


• Correct concurrent hypomagnesaemia (magnesium chloride 0.2 mmol/kg over 1 h)



Maintenance




• Treat underlying condition (see text)



* Note: Extravasation of IV calcium causes skin and subcutaneous tissue necrosis.


Late neonatal hypocalcaemia usually presents as tetany after the first few days of life. The main cause is transient hypoparathyroidism, as demonstrated by high plasma phosphate and low serum PTH concentrations in the face of hypocalcaemia. A similar clinical picture is seen in infants of mothers with hyperparathyroidism and in infants with congenital heart disease. Treatment may involve calcium infusion, calcitriol, oral calcium supplementation and a low-phosphate formula. The infant can often be weaned from this treatment after a few weeks. Persistence of the hypocalcaemia beyond this time should prompt a search for other causes of hypoparathyroidism, such as DiGeorge syndrome (aplasia of the parathyroids, thymic aplasia with T-cell immunodeficiency and cardiovascular abnormalities), hypomagnesaemia or idiopathic congenital hypoparathyroidism. An abnormality of the calcium- sensing receptor on the parathyroid cells (an activating mutation decreasing PTH release) is also a cause. Treatment is based on the use of calcitriol, often in combination with phosphate restriction.


Late-onset hypoparathyroidism may occur with destructive injury of the parathyroids (copper deposition in Wilson disease, iron deposition in haemosiderosis, or autoimmune type I polyglandular syndrome). In this latter condition, children, usually girls, present with tetany or convulsions, and may have candidiasis and adrenal insufficiency or other autoimmune disorders such as alopecia, malabsorption, thyroiditis and diabetes. Pseudohypoparathyroidism is due to end-organ resistance to PTH, and blood levels of PTH are high. Mental deficiency and skeletal abnormalities (particularly a short fourth metacarpal) may be associated. Treatment is the same as for hypoparathyroidism.



image Practical points



Hypocalcaemia




• Suspect symptomatic hypocalcaemia with tetany, unexplained stridor, irritability or convulsions.


• Confirm diagnosis with total and ionized calcium concentrations and draw blood for estimation of magnesium, phosphate and parathyroid hormone concentrations.


• Treat symptomatic hypocalcaemia with IV 10% calcium chloride 0.2 mL per kg per dose given slowly into a well-placed IV line, and monitor the ECG.

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  4. The newborn infant: stabilization and examination

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Aug 4, 2016 | Posted by in PEDIATRICS | Comments Off on Bone mineral disorders

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