11/13/24, 7\:31 PM Guide | Bone profile interpretation

Bone pro

Table of contents

Introduction

A bone pro
Serum calcium
Serum phosphate
Serum albumin
Alkaline phosphatase (ALP)
This guide gives an overview of the tests included in a bone pro

Why request a bone pro

A bone pro
To diagnose and monitor disorders of the bone (e.g. osteomalacia, Paget’s disease, bony metastases)
To diagnose and monitor cases of hypocalcaemia or hypercalcaemia
To investigate otherwise unexplained symptoms, such as fatigue or pain

Reference ranges

Table 1. Bone pro
Test Reference range
Calcium (total / corrected) 2.2 – 2.6 mmol/L
Phosphate 0.8 – 1.5 mmol/L
Albumin 35-50 g/L
Alkaline phosphatase (ALP) 30-130 U/L
Corrected calcium
1
Around 40% of calcium is bound to albumin in the bloodstream, and in this form, it is physiologically inactive. The
remaining 60% is known as ionised or ‘free’ calcium, which is physiologically active.
In severe hypoalbuminaemia, the total calcium level may appear normal, yet ionised (‘free’) calcium levels (which are
physiologically active) can be markedly increased due to decreased albumin binding. Conversely, if serum albumin
levels are raised, the total calcium level may be high, but the serum ionised calcium level may be normal due to
increased albumin binding.
Therefore, most laboratories report a ‘corrected calcium’ alongside total calcium, in which the serum calcium level is
adjusted for the serum albumin level.
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Calcium

Ionised calcium (Ca 2+
) plays a crucial role in many bodily functions, including\:
Bone formation and turnover
Muscle contraction (including myocardial function)
Blood coagulation
Disruptions in calcium homeostasis can thus cause extensive physiological disturbance.

Calcium homeostasis

Three main processes determine serum calcium level\: intestinal absorption, renal excretion and bone turnover.
Intestinal absorption
Calcium is absorbed from the small intestine in a process predominantly regulated by vitamin D. Vitamin D de
decreased calcium absorption from the gut.
Renal excretion
The kidneys regulate the amount of calcium excreted in the urine by altering calcium reabsorption in the distal tubules. This
process is regulated by parathyroid hormone (PTH). Increased PTH levels lead to decreased levels of renal calcium excretion.
Bone turnover
Bone is constantly being remodelled, with old bone broken down and new bone formed. Calcium is released from old bone
and taken up by new bone. Once again, this process is regulated by parathyroid hormone (PTH). Increased PTH levels lead to
increased calcium resorption from the bone into the bloodstream.
Parathyroid hormone (PTH)
Reference range\: 1.6 - 6.9 pmol/L
Parathyroid hormone plays a key role in calcium homeostasis. The parathyroid glands are found just posterior to the
thyroid and act to secrete PTH in response to hypocalcaemia (or low vitamin D).
PTH then directly increases serum calcium levels by decreasing renal excretion of calcium and increasing calcium
resorption from bone. PTH also indirectly increases calcium levels by increasing Vitamin D activation in the kidney, thus
increasing calcium absorption from the small intestine.
Secretion of PTH will lead to increased serum calcium levels. When serum calcium levels rise, a negative feedback
mechanism exists to decrease PTH release from the parathyroid glands, keeping serum calcium regulated.

Hypercalcemia

Hypercalcemia is de
Aetiology
Causes of hypercalcaemia include\:
Excessive PTH\: primary hyperparathyroidism, tertiary hyperparathyroidism, ectopic PTH secretion (rare)
Malignancy\: myeloma, bony metastases, paraneoplastic syndromes
Excess vitamin D\: exogenous excess / granulomatous disease (e.g. sarcoidosis)
Excess calcium intake\:
‘milk-alkali’ syndrome
Renal disease\: severe acute kidney injury
Drugs\: thiazide diuretics / lithium
Hereditary\: familial hypocalciuric hypercalcaemia
Hint\: Over 90% of cases of hypercalcemia are due to either primary hyperparathyroidism or malignancy. The next step is
always to request a PTH. PTH levels will be raised in primary hyperparathyroidism but suppressed in malignancy (due to the
negative feedback mechanism described above).
Clinical features
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Hypercalcemia may be asymptomatic. However, if symptoms develop, they are commonly remembered as ‘bones, renal
stones, abdominal groans and psychic moans’
\:
Bones\: bone pain, pathological fractures
Renal stones\: presenting with renal colic
Abdominal groans\: abdominal pain, vomiting, constipation, pancreatitis
Psychic moans\: confusion, hallucination, lethargy, depression
The ECG will classically show a shortened QT interval, and this can progress to cause complete AV nodal block and cardiac
arrest.
Management
The management of hypercalcemia initially involves reducing serum calcium levels with aggressive IV
(normal saline) whilst investigating and managing the underlying cause. Hypercalcemia refractory to rehydration may require
bisphosphonates.

Hypocalcaemia

Hypocalcaemia is de
Aetiology
2
Causes of hypocalcaemia include\:
PTH de
neck irradiation); severe hypomagnesemia (impairs PTH secretion)
Vitamin D de
Acute pancreatitis
Drugs\: bisphosphonates, calcitonin
Hint\: Requesting a PTH level is also the essential ‘next step’ test to investigate hypocalcaemia. Without PTH de
should be raised as the body attempts to restore homeostasis.
Clinical features
Hypocalcaemia may be asymptomatic or present with non-speci
Muscle weakness/cramps
Muscle tetany/spasm
Perioral paraesthesia
Psychological disturbance
Seizures
There are pathognomonic clinical signs of hypocalcaemia related to muscle tetany\:
Trosseau’s sign\: occlusion of the brachial artery (e.g. with a blood pressure cu
hand/wrist
Chvostek’s sign\: tapping over the facial nerve causes contraction of facial nerves
The ECG may show QT prolongation, which can progress to torsades de pointes and cardiac arrest.
Management
The management of hypocalcaemia involves replacing calcium whilst investigating and managing the underlying cause. For
mild or moderate symptoms, oral calcium replacement is often su
ECG changes are present, urgent IV calcium gluconate is indicated.

Phosphate

4 -
Phosphate [PO ] is an inorganic molecule comprising a central phosphorous atom and four oxygen atoms. Phosphate is a
major component of bone and plays a key role in cellular energy production (ATP) and function.
Serum phosphate level requires less tight homeostatic control than serum calcium. In normal conditions, serum phosphate
level is mainly determined by the kidney’s ability to excrete phosphate. 3
Parathyroid hormone (PTH) is also involved in
phosphate homeostasis and acts to increase renal excretion of phosphate.
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Hyperphosphataemia

Hyperphosphataemia can have various pathological consequences, including cardiovascular disease (secondary to vascular
calcichronic kidney
disease.
Most patients will be asymptomatic. Severe hyperphosphatemia can present with altered mental status, muscle weakness,
muscle pain, and even seizures.
Aetiology
Causes of hyperphosphataemia include\:
Renal impairment\: chronic kidney disease is the most common cause of hyperphosphatemia, with phosphate excretion
markedly impaired as the eGFR falls below 25
Acute phosphate load\: tumour lysis syndrome, rhabdomyolysis, exogenous phosphate-containing laxatives
Excessive phosphate resorption\: hypoparathyroidism, drugs (e.g. bisphosphonates)
Management
Acute hyperphosphatemia will generally self-resolve within 6-12 hours if renal function is normal and may need no speci
treatment. Intravenous saline can be used to help accelerate phosphate excretion. Severe cases are often associated with
signi
In chronic hyperphosphatemia (e.g. due to CKD), treatment is focused on decreasing phosphate intake (dietary modi
and absorption (phosphate-binding medications).

Hypophosphatemia

Hypophosphatemia is most commonly an incidental
delirium, seizures and coma.
Aetiology
4
Causes of hypophosphataemia include\:
Decreased absorption\: inadequate intake, medications (e.g. antacids or phosphate binders), chronic diarrhoea
Increased urinary excretion\: hyperparathyroidism, vitamin D de
Internal redistribution\: refeeding syndrome (phosphate shifts intracellularly), hungry-bone syndrome (increased calcium and
phosphate deposition in bone post parathyroidectomy)
Renal replacement therapy
Management
Most cases of hypophosphataemia are mild and can safely be managed with oral phosphate replacement. IV replacement is
indicated if the de
underlying cause.

Albumin

Albumin is the most abundant circulating protein in the bloodstream, making up around half of the total protein content.
5
Albumin is synthesised by the liver. Its functions include maintaining plasma oncotic pressure and transporting various
substances in the bloodstream, such as cations, fatty acids and exogenous drugs.
Hint\: Albumin is mainly reported in the bone pro
as part of liver function tests as it is a marker of the synthetic function of the liver.

Hypoalbuminemia

Low albumin levels in the blood generally arise from either decreased albumin production or increased albumin loss.
Albumin levels can fall due to\:
Decreased albumin production\: malnutrition, severe liver disease
Increased albumin loss\: protein-losing enteropathies, nephrotic syndrome
Hypoalbuminemia can lead to widespread oedema, as loss of oncotic pressure in the blood leads to
interstitium.
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The management generally involves identifying and treating the underlying cause, with human albumin solution (HAS)
replacement reserved for speci

Hyperalbuminemia

Raised albumin levels in the blood are relatively rare and may be seen in cases of severe dehydration or excessive protein
intake.

Alkaline phosphatase (ALP)

Serum alkaline phosphatase (ALP) is derived from biliary epithelial cells (cells lining the biliary tract) and bone turnover.
Raised ALP levels can therefore be suggestive of cholestasis or bone disease.
6
Hint\: Cholestasis describes an interruption in bile
Medics guide to liver function test interpretation.
To di
liver function tests and is found in hepatocytes and biliary epithelial cells. It is a non-speci
liver damage and cholestasis\:
An ALP rise with normal GGT suggests increased bone turnover
An ALP rise with associated GGT rise is more suggestive of cholestasis

Causes of an isolated ALP rise (normal GGT)

This is most likely due to bone pathology and may include\:
Paget’s disease of the bone
Bony metastases
Osteomalacia (Vitamin D de
Healing fractures
Serum ALP will also be physiologically raised in children and adolescents as well as in the third trimester of pregnancy.

Summary table

The bone pro
Table 1. Diagnosis of common bone disorders.
Calcium Phosphate ALP PTH
Primary
hyperparathyroidism
↑ ↓ ↑ ↑
Bony metastases ↑ N ↑ ↓
Paget's disease N N ↑ N
Osteoporosis N N N N
Osteomalacia N / ↓ N / ↓ ↑ N / ↑

References

1. UpToDate. D i a g n o s t i c a p p r o a c h t o h y p e r c a l c e m i a . November 2022. Available at [LINK].
2. UpToDate. E t i o l o g y o f h y p o c a l c e m i a i n a d u l t s . August 2022. Available at [LINK].
3. 6. UpToDate. O v e r v i e w o f t h e c a u s e s a n d t r e a t m e n t o f h y p e r p h o s p h a t e m i a . April 2023. 4. StatPearls. H y p o p h o s p h a t e m i a . December 2022. Available at [LINK].
5. StatPearls. P h y s i o l o g y , A l b u m i n . January 2023. Available at [LINK].
UpToDate. A p p r o a c h t o t h e p a t i e n t w i t h a b n o r m a l l i v e r b i o c h e m i c a l a n d f u n c t i o n t e s t s . Available at [LINK].
April 2022. Available at [LINK].
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