Biochemical Diagnosis of Bone Metabolism(2013)

1、Biochemical Diagnosis of Bone MetabolismCheng XiaohuanZhongnan HospitalContents Calcium regulation Hypercalcaemia and Hypocalcaemia Phosphate and magnesium Bone metabolism OsteoporosisCalcium homeostasis Calcium exists in bone , ECF, gut and kidney. The amount of calcium lying in different compartme

2、nt is not static. The following figure shows normal calcium balance in the body.Unbound calciumBound calciumDiffusible bound calciumProteinbound calciumSerum calcium(50%)(10%)(40%)Diffusible calciumNon-diffusible calcium(biologically active fraction)(Albumin) total serum calcium:2.25-2.75mmol/L Unbo

3、und calcium:1.10-1.34mmol/L binding is pH dependentpH Ca2+pH Ca2+Maintenance of unbound calcium concentration Nerve function Membrane permeability Muscle contraction Glandular secretionCalcium regulation Mainly by PTH It is the unbound calcium concentration that is recognized by the parathyroid glan

4、ds. secreted from the parathyroid glands in response to a low unbound plasma calcium. Clinically, total calcium , not the unbound calcium is detected. This gives rise to a problem in the interpretation of results. Next figure can explain the contradictory circumstances.CALCIUM REGULATION Adjusted ca

5、lcium (mmol/l)=total measured calcium +0.02(47-albumin) The measured calcium is adjusted by 0.1 mmol/L for every 5 g/L that albumin is less than 47HYPOCALCAEMIA Calcium 2.25mmol/L Or Ca2+ 2.75mmol/LAetiology Parathyroid adenoma（腺瘤） primary hyperparathyroidism（甲状旁腺功能亢进）PTH increased Malignancy（恶性肿瘤）:

6、 some tumors secrete PTHrPClinical features Neurological and psychiatric features : lethargy, confusion, irritability and depression Gastrointestinal problems : anorexia(厌食), abdominal pain, nausea and vomiting, and constipation(便秘) Renal features : thirst and polyuria, and renal calculi(结石) Cardiac

7、 arrhythmias（心律失常）（心律失常）PHOSPHATE intake 40mmol/day excretion by faeces(粪便)14mmol/day; urine 26mmol/day body distribution: bone 17000mmol; soft tissue 3000mmol; plasma 1mmol/lPlasma inorganic phosphate phosphate exists in the ECF both as monohydrogen phosphate and as dihydrogen phosphate total conce

8、ntration : 0.80-1.40mmol/l about 20% of plasma phosphate is attached to protein in plasma ,calcium and phosphate have a reciprocal relationship(Ca*P=36-40)MAGNESIUM Intracellular functionMg2+ second abundant cations after K+some 300 enzyme systems are Mg2+ activated intracellular biochemistry ： glyc

9、olysis（醣酵解）, oxidative metabolism, transmembrane（横跨膜的）transport of potassium and calcium Extracellular functionaffect electrical properties of cell membranesinteractions between Mg2+ , K2+and Ca2+influence the secretion of PTHsevere hypomagnesaemia may cause hypoparathyroidism（甲状旁腺功能减退）Homeostasis I

10、ntake from mainly green vegetables are around 300mg/day About 30% of the dietary absorbed from the small intestine Distributed to active tissue(bone 750mmol; soft tissue 450mmol; ECF 15mmol) Urine excretion 5-10mmol/day Serum magnesium Hypermagnesaemia is uncommon , occasionally seen in renal failur

11、e Hypomagnesaemia similar to hypercalcaemia: imparied neuromuscular function such as tetany, hyperirritability(应激过度); tremor; convulsion and muscle weaknessBone metabolismBone metabolism Biochemical markers of bone resorption and bone formation to assess the extent of disease and monitor treatment M

12、onitor bone formation:Osteocalcin(OC,骨钙素)Bone alkaline phosphatase (B-ALP，骨碱性磷酸酶)PICP（型前胶原肽） Monitor bone resorption:TRAP（抗酒石酸酸性磷酸酶）Gal-Hyl（尿半乳糖羟赖氨酸） 型胶原交联降解产物Bone diseaseCommon bone disorders: Osteoporosis(OP,骨质疏松症) Osteomalacia（骨软化）and rickets（佝偻病）Biochemistry testing in calcium disorders or bone

13、diseaseFirst line tests in a serum : calcium albumin phosphate alkaline phosphatase（ALP）Follow-up teses : PTH Magnesium Urine calcium excretion 1，25-hydroxycholcalciferol Urine hydroxyproline excretion OsteocalcinOSTEOPOROSISCharacters: Reduction in bone mass per unit volume Composition of the matri

14、x is normal, but less of it Cortical（皮质的）areas are thinner and the trabeculae（骨小粱）are smaller and less extensiveAetiology Primary osteoporosisthis aetiology is unknown. But both sexes show a gradual bone loss throughout life but women loss bone rapidly in the postmenopausal years Secondary osteoporo

15、sis: Certain drugs,especially long-term use of corticosteroids（皮质类固醇） or heparin（肝素）immobilizationsmoking alcohol Cushings syndromegonadal failure(性腺生成障碍)hyperthyroidismgastrointestinal disease Diagnosis Vertebral（脊椎的）compression fracture Distal radius fracture Neck of femur(股骨)fracture Vertebrae crush fracture may occur slowlyClinical biochemistry labotatory Biochemical t