BONE DISEASE FOR R2. By.. Rungnapa Laortanakul

Transcription

1 BONE DISEASE FOR R2 By.. Rungnapa Laortanakul

2 Bone Mineral Metabolism Hypercalcemia Hypocalcemia Vitamin D deficiency Basic Bone Biology Osteoporosis Osteomalacia

3 Vitamin D synthesis and metabolism Previtamin D3 vitamind3 via thermal isomerization UVB Skin Major source circulation

4 Parathyroid hormone Vitamin D

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6 PTH action Hypocalcimia stimulate PTH secretion Bone bone resorption Ca,PO 4 Kidney Ca resorption PO 4 excretion Calcitriol Net effect is Ca PO 4

7 Calcitriol 1,25-dihydroxyvitamin D Small intestine resorption of Ca,PO 4 Bone bone resorption Kidney excretion of Ca,PO 4 Net effect is Ca PO 4

8 Hypercalcemia Clinical depend on time onset and level Normal level is mg/dl Calcium level mg/dl asymptomatic Calcium level >12 usually symptomatic

9 Clinical presentation Renal Nephrolithiasis/ Nephrocalcinosis Nephrogenic DI Polydipsia/ Polyuria Distal RTA Renal insufficiency Chronic hypercalcemic nephropathy nephrocalcinosis

10 GI Constipation, Anorexia, Abdominal pain, Pancreatitis, Increase gastrin secretion PU CNS Anxiety, Depression, Cognitive dysfunction, Confuse, Psychosis, Coma CVS Calcify valve, HT, Shortened QT interval Skeleton Gout, Pseudogout, Chondrocalcinosis, Osteoporosis, Osteopenia, Osteitis fibrosa cystica

11 Causes of hypercalcemia Parathyroid-dependent hypercalcemia 1 hyperparathyroidism 3 hyperparathyroidism Familial hypocalciuric hypercalcemia Lithium-associated Antagonist autoantibodies to the calcium-sensing receptor Williams texbook 11th ed.

12 Parathyroid-independent hypercalcemia Neoplasm -PTHrP dependent -Other humoral syndromes -Local osteolytic dz (including metastasis) PTHrP excess (non-neoplasia) Excess vit D action -Ingestion of excess vit D or vit D analogues -Topical vit D analogues -Granulomatous dz -Williams syndrome Thyrotoxicosis Adrenal insufficiency Renal failure -ARF -CRF with aplastic bone dz Immobilization Jansen s dz Drugs : vit A intoxication milk-alkali syndrome thiazide diuretics theophylline Williams texbook 11th ed.

13 Hyper Ca Ionized Ca High Clinical evaluation Hx,PE, e lyte,bun,cr,po 4,ALP Normal Hemoconcentration or Serum protein abnormality S&S malignancy Normal or high S.PTH Low Search for occult malignancy Chest radiograph Serum/urine IEP Mammogram Abdominal/chest CT PTH dependent PTH independent Evaluate for Other causes of PTH-independent Select appropriate tx, consider bisphosphonate

14 PTH dependent YES 24-hr urine calcium & Cr U ca < 100 mg/day or Cl ca /Cl cr < 0.01 NO PTH normal PTH high 1 hyperparathyroidism Li therapy Age<40 or Family hx YES NO BMD Review criteria Ca High Stop Li Ca normal Presumptive FHH; Consider family screening For surgery Li induce hyperpth

15 Work up Ca, PO 4 level Film find evidence of bone abnormality Find the solid organ tumor eg. CXR Alkaline phosphatase bone lysis Hyperchloric metabolic acidosis suggest hyperpth TFT hyperthyroidism Cortisol adrenal insufficiency Intact PTH level hyperparathyroidism PTH-rP, vit D Urine calcium

16 Primary hyperparathyroidism Present in one of four ways: 1. Asymptomatic hypercalcemia detected by routine biochemical screening 2. Symptomatic hypercalcemia 3. During evaluation for manifestations of hyperparathyroidism such as osteopenia, osteoporosis, or nephrolithiasis 4. Rarely, hyperparathyroid bone disease (osteitis fibrosa cystica) or parathyroid crisis

17 Primary hyperparathyroidism Adenoma Carcinoma Glandular hyperplasia MEN 1 MEN 2A Familial hyperparathyroidism

18 Multiple endocrine neoplasia Type 1 Primary hyperparathyroidism (>90 percent) Pituitary tumors (10 to 20 percent) Prolactinoma Growth hormone-secreting Corticotropin-secreting Non-hormone-secreting Enteropancreatic tumors (60 to 70 percent) Gastrinoma (Zollinger-Ellison syndrome) Insulinoma Vasoactive-intestinal polypeptidesecreting Glucagonoma Pancreatic polypeptide-secreting Non-hormone-secreting Other Type 2A Medullary thyroid cancer (>90 percent) Pheochromocytoma (40 to 50 percent) Parathyroid hyperplasia (10 to 20 percent) Cutaneous lichen amyloidosis Type 2B Medullary thyroid cancer Pheochromocytoma Other -Mucosal neuromas -Intestingal ganglioneuromas -Marfanoid habitus Familial medullary thyroid cancer (variant of 2A) Medullary thyroid cancer

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20 Band keratopathy Subepithelial Ca-PO 4 deposits in the cornea

21 Sub-periosteal resorption

22 Cystic brown tumors Chondrocalcinosis

23 National Institutes of Health Consensus Conference in 2008 Asymptomatic PHPT candidates for surgery Age < 50 yr Serum calcium level 1.0 mg/dl (0.25 mmol/liter) above upper limits of normal Cr.Cl reduced to 60 ml/min by MDRD equation no.7 Osteoporosis by T-score History of kidney stones or fractures J Clin Endocrinol Metab 94: , 2009

24 Symptomatic PHPT Cohort studies : after parathyroidectomy BMD & fracture rate : improve Cognitive function:improve Kidney stones : incidence declines after surgery. CVD & premature death : decrease

25 Sestamibi scan Noninvasive Most popular Localize abnormal parathyroid glands Quality varies Nonlocalizing sestamibi -Multigland disease -Small parathyroid gl. -Coexistent thyroid dz.

26 Secondary and tertiary hyperparathyroidism 2 hyperparathyroidism Severe chronic kidney disease Usually have low or normal serum calcium concentrations Prolonged disease, may develop hypercalcemia 'Adynamic bone disease 3 hyperparathyroidism Advanced renal failure Due to progression from appropriate parathyroid hyperplasia to autonomous overproduction of PTH UTD18.1

27 Milk-alkali syndrome Triad of hypercalcemia, metabolic alkalosis, and renal insufficiency Associated with the ingestion of large amounts of calcium and absorbable alkali Typically occurs in the setting of excess calcium carbonate supplementation to treat osteoporosis or dyspepsia UTD18.1

28 Milk-alkali syndrome Metabolic alkalosis can directly stimulating calcium reabsorption in the distal tubule, thereby diminishing calcium excretion Calcium-induced decline in renal function, due to renal vasoconstriction Chronic hypercalcemia, renal structural injury, can also contribute to the inability to excrete the excess calcium Renal function usually returns to baseline after cessation of milk or calcium carbonate intake, but irreversible injury can occur in patients who have prolonged hypercalcemia UTD18.1

29 Milk-alkali syndrome What remains unexplained is the apparent difference in sensitivity of individuals to increased intake of calcium and alkali Some individuals may not suppress calcitriol levels in response to large doses of calcium carbonate UTD18.1

30 Malignancies associated with hypercalcemia Osteolytic metastases: Breast cancer Multiple myeloma Lymphoma Leukemia Humoral hypercalcemia (PTHrP): Squamous cell carcinomas Renal carcinomas Bladder carcinoma Breast cancer Ovarian carcinoma Non-Hodgkin lymphoma CML Leukemia Lymphoma 1,25- dihydroxyvitamin D: Lymphoma (Non-Hodgkin, Hodgkin, lymphomatosis/granulomatosis) Ovarian dysgerminomas Ectopic PTH sectretion: Ovarian carcinoma Lung carcinomas Neuroectodermal tumor Thyroid papillary carcinoma Rhabdomyosarcoma Pancreatic cancer UTD18.1

31 Treatment of hypercalcemia Saline therapy Loop diuretic Initiated routinely once fluid repletion had been achieved to further increase urinary calcium excretion Calcitonin Bisphosphonate Dialysis UTD18.1

32 Calcitonin Reduce serum calcium by increasing renal calcium excretion Decreasing bone reabsorption via interference with osteoclast maturation Salmon calcitonin (4 international units/kg) is usually administered IM or SC every 12 hour Limited to first 48 hours, even with repeated doses, indicating the development of tachyphylaxis, perhaps due to receptor downregulation UTD18.1

33 Bisphosphonates Intravenous zoledronic acid or pamidronate Side effects Flu-like symptoms (fever, arthralgias, myalgia, fatigue, bone pain) Ocular inflammation (uveitis) Hypocalcemia Hypophosphatemia Impaired renal function/nephrotic syndrome Osteonecrosis of the jaw UTD18.1

34 Glucocorticoid Responsible for the hypercalcemia associated Excess ingestion of vitamin D Endogenous overproduction of calcitriol (1,25-dihydroxyvitamin D) Chronic granulomatous diseases eg, sarcoidosis Lymphoma UTD18.1

35 Hypocalcemia Clinical manifestations of hypocalcemia depend upon the severity and chronicity of hypocalcemia Each 1 g/dl reduction in the serum albumin concentration will lower the total calcium concentration by approximately 0.8 mg/dl

36 Clinical manifestations of hypocalcemia Acute Neuromuscular irritability (Tetany) Paresthesias (peri-oral, extremities) Muscle twitching Carpopedal spasm Trousseau's sign Chvostek's sign Seizures Laryngospasm Bronchospasm Cardiac Prolonged QT interval Hypotension Heart failure Arrhythmia Papilledema Chronic Ectopic calcification (basal ganglia) Extrapyramidal signs Parkinsonism Dementia Subcapsular cataracts Abnormal dentition Dry skin

37 Major causes of hypocalcemia Low PTH (hypoparathyroidism) Genetic disorders Abnormal parathyroid gland development Abnormal PTH synthesis Activating mutations of calcium sensing receptor (autosomal dominant hypocalcemia or sporadic isolated hypoparathyroidism) Post-surgical : thyroidectomy, parathyroidectomy, radical neck dissection Autoimmune Autoimmune polyglandular syndrome (associated with chronic mucocutaneous candidiasis and primary adrenal insufficiency) Isolated hypoparathyroidism due to activating antibodies to calcium sensing receptor Infiltration of the parathyroid gland : granulomatous, iron overload, metastases Radiation induced destruction parathyroid glands Hungry bone syndrome (post parathyroidectomy) HIV infection UTD18.1

38 Major causes of hypocalcemia Low PTH (hypoparathyroidism) Genetic disorders Abnormal parathyroid gland development Abnormal PTH synthesis Activating mutations of calcium sensing receptor (autosomal dominant hypocalcemia or sporadic isolated hypoparathyroidism) Post-surgical : thyroidectomy, parathyroidectomy, radical neck dissection Autoimmune Autoimmune polyglandular syndrome (associated with chronic mucocutaneous candidiasis and primary adrenal insufficiency) Isolated hypoparathyroidism due to activating antibodies to calcium sensing receptor Infiltration of the parathyroid gland : granulomatous, iron overload, metastases Radiation induced destruction parathyroid glands Hungry bone syndrome (post parathyroidectomy) HIV infection

39 Major causes of hypocalcemia High PTH (secondary hyperparathyroidism in response to hypocalcemia) Vitamin D deficiency or resistance Parathyroid hormone resistance Pseudohypoparathyroidism Hypomagnesemia Renal disease Loss of calcium from the circulation Hyperphosphatemia Tumor lysis Acute pancreatitis Osteoblastic metastases Acute respiratory alkalosis Sepsis or acute severe illness Drugs Inhibitors of bone resorption (bisphosphonates, calcitonin), especially in vitamin D deficiency Cinacalcet Calcium chelators (EDTA, citrate, phosphate) Foscarnet (due to intravascular complexing with calcium) Phenytoin (due to conversion of vitamin D to inactive metabolites) Fluoride poisoning Disorders of magnesium metabolism Hypomagnesemia can reduce PTH secretion or cause PTH resistance and is therefore associated with normal, low, or high PTH levels UTD18.1

40 Approach to hypocalcemia Measure serum albumin Family history of hypocalcemia genetic cause Chronic hypocalcemia Activating mutation of calcium sensing receptor Pseudohypoparathyroidism Acquired hypoparathyroidism Postsurgical or autoimmune damage Autoimmune hypoparathyroidism Isolated abnormality/polyglandular autoimmune syndrome type I Lab : ipth, Cr, Mg, PO4, 25(OH) vitd UTD18.1

41 N Engl J Med 2004;350:

42 PTH Correct Ca PO4 Mg 25(OH)D 1,25(OH)D Cr Hypoparathyroid Activating mutation calcium sensing receptor Hypo Mg PTH resistance (pseudohypoparathyroid) Vitamin D deficiency Chronic kidney disease UTD18.1

43 PTH Correct Ca PO4 Mg 25(OH)D 1,25(OH)D Cr Hypoparathyroid Activating mutation calcium sensing receptor Hypo Mg PTH resistance (pseudohypoparathyroid) Vitamin D deficiency Chronic kidney disease UTD18.1

44 Osteoporosis Decrease bone strength and increase fracture Imbalance of bone resorption and bone formation Bone strength Structural properties : Size, Shape, Microarchitecture Material properties : Mineral, Collagen

45 WHO definition of Osteoporosis Diagnostic Category T-score Normal > -1 Osteopenia -1 to -2.5 Osteoporosis -2.5 Severe Osteoporosis -2.5 and 1 fragility fracture

46 ข อบ งช ในการส งตรวจ BMD Thai osteoporosis guideline

47 Thai osteoporosis guideline

48 BMD (DEXA) Central Lumbar spine (L1-L4) Femoral area Peripheral Radius

49 BMD

50 BMD

51 BMD

52 BMD

53 Common causes for secondary osteoporosis Endocrine diseases Diabetes mellitus GH deficiency (rare) Acromegaly (rare) Hypercortisolism Hyperparathyroidism Hyperthyroidism Premature menopause Male hypogonadism GI disorders Gastrectomy Celiac disease Inflammatory bowel disease Liver cirrhosis Chronic biliary tract obstruction Chronic therapy with proton pump inhibitors European Journal of Endocrinology (2010)

54 Common causes for secondary osteoporosis Hematologic diseases Myeloma Monoclonal gammopathy of undetermined significance Lymphoma/leukemia Systemic mastocytosis (rare) Disseminated carcinoma Chemotherapy Rheumatological Rheumatoid arthritis Ankylosing spondylitis Systemic lupus erythematosus Other Osteogenesis imperfecta Anorexia nervosa European Journal of Endocrinology (2010)

55 Glucocorticoid excess Glucocorticoids impairs skeletal health Inhibition of bone formation due to induction of osteoblast and osteocyte apoptosis European Journal of Endocrinology (2010)

56 Glucocorticoid excess Predominant spinal bone loss and vertebral fractures Increased risk of falls due to muscular atrophy and altered neuromuscular function Low doses of glucocorticoids (prednisolone mg/day) associated with a 2.6-fold higher risk of vertebral fractures European Journal of Endocrinology (2010)

57 Glucocorticoid-induce Osteoporosis N Engl J Med 2011;365:62-70

58 Glucocorticoid-induce Osteoporosis National osteoporosis foundation Prednisolone 5 mg/day for at least 3 months Yearly BMD testing Threshold for treatment : T-score 2.5 Calcium 1200 mg/day, vitamin D 2000 units/day Bisphosphonate Teriparatide : only for patients at high risk N Engl J Med 2011;365:62-70

59 Hyperthyroidism Thyroid hormone excess (suppressed TSH) Activation of thyroid hormone receptor a on osteoblasts and osteoclasts results in enhanced bone resorption and bone loss European Journal of Endocrinology (2010)

60 Hyperthyroidism Large study of 686 postmenopausal women serum TSH level < 0.1 miu/l 4x 5x risk of hip and vertebral fractures Meta-analysis of 21 studies indicated that thyroid hormone therapy for TSH suppression in differentiated thyroid cancer subclinical hyperthyroidism is associated with osteoporosis in postmenopausal women European Journal of Endocrinology (2010)

61 Drug-induced osteoporosis Numerous drugs affect bone metabolism interfere Absorption of vitamin D, Ca, and PO 4 Vitamin D metabolism and action Direct cellular effects on osteoblasts, osteoclasts, and osteocytes Interference amount or quality of bone matrix proteins European Journal of Endocrinology (2010)

62 Drug-induced osteoporosis TZDs (rosiglitazone and pioglitazone) Insulin sensitizers Act as agonists of the peroxisome proliferatoractivated receptor-gamma 3-5 fold higher risk of fractures of the humerus, femur, and hip in postmenopausal women European Journal of Endocrinology (2010)

63 Drug-induced osteoporosis TZD Shunting pluripotent mesenchymal stem cells Osteoblastic lineage Adipocyte European Journal of Endocrinology (2010)

64 Drug-induced osteoporosis Drug class Examples Indications Glucocorticoids Prednisolone Autoimmune diseases Chemotherapeutic drugs Methotrexate, ifosfamide Tyrosine kinase inhibitors Imatinib Chronic myelogenous leukemia Thiazolidinediones Rosiglitazone, pioglitazone Type 2 diabetes mellitus Proton pump inhibitor Omeprazole and pantoprazole Peptic ulcer and reflux diseases Thyroid hormone L-thyroxine Replacement therapy for hypothyroidism, thyroid cancer Anticonvulsants Valproic acid Chronic seizure disorders Antidepressants Selective serotonin reuptake inhibitors Chronic depression Anti-retroviral drugs Tenofovir HIV disease European Journal of Endocrinology (2010)

65 Diagnostic tests in the work-up of secondary osteoporosis Diagnostic tests CBC Renal and Liver function test Ca and PO 4 Serum bone specific or ALP Serum 25-hydroxyvitamin D Serum TSH FBS Intact PTH Serum protein electrophoresis, immunofixation Purpose Anemia as in myeloma or celiac disease, Leukocytosis as in leukemia Renal or liver failure, alcohol abuse Primary hyperparathyroid, myeloma Paget disease, osteomalacia Vitamin D deficiency, osteomalacia Hyperthyroidism Diabetic mellitus Primary hyperparathyroidism MGUS, myeloma European Journal of Endocrinology (2010)

66 Diagnostic tests Serum free testosterone Serum CRP Diagnostic tests in the work-up of secondary osteoporosis Purpose Male hypogonadism 24 hour urine calcium excretion Hypercalciuria Anti-tissue transglutaminase antibodies Anti-HIV antibodies Morning fasting serum cortisol after dexamethasone suppression Serum tryptase levels, urinary histamine excretion COL1A genetic testing Iliac crest bone biopsy Chronic infection/inflammation Celiac disease HIV disease, AIDS Cushing s syndrome Systemic mastocytosis Osteogenesis imperfecta Systemic mastocytosis, MGUS/myeloma, osteomalacia, lymphoma/leukemia European Journal of Endocrinology (2010)

67 Laboratory Evaluation CBC Renal function Chemistry : Ca, PO 4, ALP, LFT ESR, CRP Thyroid function test 25- hydroxyvitamin D Gonadal function

68 Treatment of Osteoporosis Pharmacotherapy Secondary cause Lifestyle Modification

69 Factor Influencing Fractures Hormone Shape & architecture Postural reflexes Nutrition Bone mass Bone strength Fracture Exercise & Life style Material properties Falls Soft tissue padding

70 Lifestyle Modification Weight-bearing exercise : jogging, aerobic dancing, jumping rope Physical activity : 30 min / most day of week Fall prevention

71 Treatment (NOF 2008) Postmenopausal women and men older than 50 yr A hip or vertebral fracture fracture T score < -2.5 at femoral neck, total hip or spine Low bone mass (T score -1 to -2.5 at femoral neck, total hip or spine) with other prior fracture Low bone mass (T score -1 to -2.5 at femoral neck, total hip or spine) with secondary causes associated with high risk fracture Low bone mass (T score -1 to -2.5 at femoral neck, total hip or spine) and 10- yr probability of hip fracture 3% or a 10-yr probability of any major osteoporosis related fracture 20%

72 การร กษาภาวะโรคกระด กพร น Thai osteoporosis guideline

73 Thai osteoporosis guideline

74 Thai osteoporosis guideline

75 Pharmacotherapy Adequate Calcium and vitamin D intake NOF 2008 : -Ca 1200 mg per day, -Vitamin D IU per day Thai : -Ca ; yr : 1000 mg per day, >50 yr : 800 mg per day -Vitamin D : IU per day

76 Which drugs should be used? Antiresorptive agents Bisphosphonate Calcitonin Hormone replacement therapy Selective estrogen receptor modulators Bone formative (anabolic) agents Teriparatide (1-34 PTH) Double action Strontium ranelate

77 Bisphosphonate Targeting of bisphosphonates to bone, localized release during osteoclastic bone resorption Intestinal absorption is low Taken with a glass of tap water and 30 min before food or other fluids 40-60% absorbed bisphosphonate not bound to bone & not metabolized Eliminated unchanged by renal excretion

78 Flu-like symptoms Bisphosphonates IV can block FPP production in monocytes Accumulation of isopentenyl diphosphate (IPP) Because IPP is also a bacterial antigen, peripheral blood T cells recognize this as bacterial infection Releasing TNF-α and IFN-γ, increasing IL-6 and CRP, and causing flu-like symptoms Associated with 1 st bisphosphonate doses

79 Esophagitis and ulceration Before absorption, bisphosphonates taken orally can bind to gastric cells Inhibition of FPP synthase rapidly leads to cell death. This may explain the ability of orally administered N-BPs to cause esophagitis and ulceration

80 Osteonecrosis of the Jaw (ONJ) Rarely with oral bisphosphonates Most cases of Pt cancer with IV bisphosphonates Risk factors -Cancer -Concomitant therapies (chemotherapy, radiotherapy and corticosteroids) -Poor oral hygiene -Comorbid eg. anemia, coagulopathy, infection -Duration of exposure, and older age CKD

81 Osteonecrosis of Jaw

82 Prevention(recommend) Before use bisphosphonates :removal of all foci of dental infection. Routine dental care Regular oral examinations

83 Osteomalacia Osteomalacia : disorder of mineralization of newly formed matrix in adults Rickets : disorder of defective mineralization of cartilage in the epiphyseal growth plates of children, leading to widening of the ends of long bones, growth retardation, and skeletal deformities.

84 Normal bone Osteoporosis Decreased bone mineralization and matrix Osteomalacia Decreased bone mineralization with normal or increased matrix Osteoporosis + osteomalacia Suggest osteomalacia Bone pain, tenderness Myopathy Pseudofracture Increased alkaline P

85 Causes of osteomalacia Abnormal vitamin D metabolism : 2 hyperparathyroidism & hypophosphatemia Deficient intake or absorption Dietary Inadequate sunlight exposure Malabsorption Gastrectomy Small bowel disease Vitamin D Pancreatic insufficiency Defective 25-hydroxylation Biliary cirrhosis Alcoholic cirrhosis Anticonvulsants Loss of vitamin D binding protein Nephrotic syndrome Defective 1-alpha 25-hydroxylation Hypoparathyroidism Renal failure Vitamin D-dependent rickets type 1 Defective target organ response to calcitriol Vitamin D-dependent rickets, type II (Hereditary vitamin D resistant rickets, HVDRR)

86 Causes of osteomalacia Mineralization defects Abnormal matrix Chronic renal failure Osteogenesis imperfecta Fibrogenesis imperfecta Axial osteomalacia Enzyme deficiency Hypophosphatasia Inhibitors of mineralization Fluoride Aluminium Bisphosphonates Phosphate deficiency Decreased intake Antacids Impaired renal reabsorption -Primary defects X-linked hypophosphatemic rickets (vitamin D resistant rickets, VDRR) Hereditary hypophosphatemic rickets with hypercalciuria Sporadic acquired hypophosphatemic rickets Fanconi Syndrome-Wilson disease, cystinosis, multiple myeloma -Secondary defects Primary hyperparathyroidism Secondary hyperparathyroidism (renal tubular acidosis, type 1 and disorders of vitamin D metabolism) Oncogenic osteomalacia

87 CLINICAL PRESENTATION Asymptomatic and present radiologically as osteopenia Proximal muscle weakness Muscle wasting, hypotonia, and discomfort with movement Waddling gait Bone pain lower spine, pelvis, lower extremities may be associated with tenderness to palpation dull & aching, aggravated by activity & weight bearing Fractures may occur with little or no trauma ribs, vertebrae, long bones Skeletal deformities are infrequent in adults. Abnormal spinal curvature or deformity of the thorax or pelvis appears only in severe osteomalacia of long duration

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89 Two theories have been proposed: 1. Stress fractures that have been repaired by the laying down of inadequately mineralized osteoid 2. Result of erosion by arterial pulsations. Looser zones : pseudofractures or narrow radiolucent lines

90 Disorder Phosphate Calcium ALP Vit D deficiency with 2 hyper PTH Low Low to low normal Elevated Metabolic acidosis Normal Normal Normal Proximal RTA Low Normal Normal Hypophosphatasia Normal Normal Low Osteogenesis imperfecta and axial osteomalacia Normal Normal Normal Osteoporosis Normal Normal Normal

91 Vitamin D deficiency 25-Hydroxyvitamin D levels are inversely associated with parathyroid hormone levels until the former reach 30 to 40 ng per milliliter, at which point PTH begin to level off (at their nadir) Vitamin D insufficiency.. 25-hydroxyvitamin D < 30 ng per milliliter Vitamin D intoxication.. 25-hydroxyvitamin D > 150 ng per milliliter

92 Treatment Preventive and Maintenance to Avoid Deficiency IU of vitamin D3/day 50,000 IU of vitamin D2 every 2 wk or every month Treatment of Deficiency 50,000 IU of vitamin D2 every wk for 8 weeks Then repeat treatment for another 8 wk if 25- hydroxyvitamin D <30 ng/ml