Metabolic Bone Disorders Prof. Mamoun Kremli AlMaarefa College

Objectives Bone as an active tissue Calcium is an important mineral Calcium metaboism – normal control Diseases Osteoporosis Rickets and Osteomalacia Hyperparathyroidism Scurvy

Functions of bone tissue Mechanical: Support & protect soft tissue Load transmission Mediate movement Mineral reservoir Largest reservoir of Ca Regulation of Ca

Basic Anatomy of Bone http://classes.midlandstech.edu/

Bone components A: Matrix: Organic: (40% of dry weight) Collagen fibers Cells Inorganic (Minerals): (60%) Ca hydroxyapetite, Ca phosphate Others B: Cells: Osteoblasts, osteoclasts, osteocytes, others

Bone cells Osteoblasts Osteoclasts Osteocytes Osteone: a unit, not a cell

Bone is active Continuous activity and flow Structure and composition changing all the time Regulations by regulating cellular activity: Osteoclasts & Osteoblasts Cellular Activity Modulation of Bone Structure & Composition Changes in mineral ion concentrations Hormones & Local Factors

Bone growth & remodelling Epiphyseal: Endochondral ossification On surface: Oppositional ossification In Adults: Remodelling of existing bone (no growth) Annually: 4% of cortical and 25% of cancellous “old bone” continuously replaced by “new bone” Initially: formation slightly exceeds resorption Later: resorption exceeds formation Bone mass steadily declines

Age related bone changes Childhood – adolescence: Growth ( size & change shape) Adolescence – 35 (40) years: Bones get heavier and stronger Annual bone mass gain: 3% 35 (40) – 50 years: Slow loss of bone mass annually: Men: 0.3% Women: 0.5% to menopause, then 3% for 10 years - (Why?) (↑ osteoclastic activity by ↓ hormones) 65 years – onwards: Loss of mass slows gradually to 0.5% (↓osteoblastic activity)

Body Calcium Most of Ca in body is present in bone Release of Ca from bone is a slow process Serum calcium is essential for cell function, nerve conduction, and muscle contraction Normal level: 8.8-10.4 mg/dl (2.2-2.6 mmol/L) S. levels have to be controlled quickly Intestinal absorption Renal reabsorption

Causes of Calcium absorption  intake of phosphates (as in soft drinks)  intake of oxalates (as in tea and coffee) Drugs: corticosteroids Intestinal malabsorption syndromes

Players in Ca regulation Vit. D is the general crude regulator Target organs: Small intestines Bones PTH is the sensitive fine regulator Kidneys (v quick) Bones (slow) (indirectly): small intestine

Players in Ca regulation Cacitonin: C cells of Thyroid Opposite PTH on bone and kidneys Oestrogen: Protects bone from PTH Corticosteroids: Bad to bone Local – BMP (Bone Morphogenic Proteins) Mechanical stress: Strengthens bone

Calcium metabolism

Hormonal regulation of Ca met.

Hormonal regulation of Ca met. Mesutti, 2011

Laboratory investigations X-rays Bone mineral density (BMD) DEXA scans: Dual Energy X0ray Absorptiometry Biochemical tests: Serum Ca, Phosphate Serum Alkalin Phosphatase Osteoclastic activity, measures bone turnover rate Vit. D levels Urine Ca and Phosphate excretion Renal profile Liver function test

Common Diseases Osteoporosis Rickets Osteomalacia Hyperparathyroidism (osteitis fibrosa)

Osteoporosis Reduction of bone mass Types: Bone minerals and matrix both reduced Matrix present is normally mineralized Types: Generalized: systemic disease Localized: disuse (e.g. in cast) http://drcecilia.ca/

Osteoporosis More in women In men: Post menopausal Oestrogen withdrawal Increased with: cigarette smoking when start menopause with weak bones In men: 15 years later In elderly, may be associated with osteomalacia

Osteoporosis – clinical features Weak bones: easily fractures: Vertebral compression fractures Backache, kyphosis Colle’s fracture Neck of femur Proximal humerus Orthopedic Radiology, A Greenspan. lippincott

Osteoporosis – clinical features Weak bones: easily fractures: Vertebral compression fractures Backache, kyphosis Colle’s fracture Neck of femur Proximal humerus http://library.med.utah.edu www.rcuv.org/tag/health Orthopedic Radiology, A Greenspan. lippincott

Osteoporosis – clinical features Weak bones: easily fractures: Vertebral compression fractures Backache, kyphosis Colle’s fracture Neck of femur Proximal humerus http://library.med.utah.edu Apley’s System of Prthop & Fractures Orthopedic Radiology, A Greenspan. lippincott

Osteoporosis – clinical features Weak bones: easily fractures: Vertebral compression fractures Backache, kyphosis Colle’s fracture Neck of femur Proximal humerus Loss of cortical thickness seen on X-rays http://library.med.utah.edu Apley’s System of Prthop & Fractures Orthopedic Radiology, A Greenspan. lippincott

Risk Factors for postmenopausal osteoporosis Caucasian (white) or Asiatic ethnicity F.H. of osteoporosis H.O. anorexia nervosa or amenorrhea Low peak bone mass in third decade Early onset menopause Very slim built Oophorectomy and early hysterectomy Nutritional deficiency Chronic lack of exercise

Osteoporosis - Prevention Good Ca and Vit. D intake Good physical activity Exposure to sun No smoking No alcohol http://dietitians-online.blogspot.com

Osteoporosis - Prevention If BMD low: Hormone replacement therapy (oestrogen): Effective early For initial five years Problems: Dysfunctional uterine bleeding Risk of uterine and breast cancer – on long use

Osteoporosis - treatment Treat the fractures Maintain good Ca and Vit D intake May be associated with osteomalacia Maintain good physical activity Trying to reduce rate of further bone loss Hormone replacement therapy Bisphosphonates

Rickets & Osteomalacia

Rickets & Osteomalacia Same disease: (children / adults) Inadequate absorption and/or utilization of Ca Common causes: Lack of Vit. D Sever Ca deficiency Hypophosphatemia Results in loss of mineralization of bone

Rickets - pathology Matrix forms, not calcified In growing physis Widened physis (epiphyseal growth plate) Cupping of metaphyseal end (weak new bone) In all bone Osteopenia, Thin cortex, Deformity Harrisons sulcus, frontal bossing In sever cases: hypocalcaemia: Tetany, convulsions, failure to thrive

Rickets – clinical picture Enlarged ends of long bones Wrists, knees Rickety rosary: costo-chondral junctions Harrisons sulcus Frontal bossing Bowing of legs: Localized – distal tibiae In sever cases: tetany, convulsions Orthopedic Radiology, A Greenspan. lippincott

Rickets – clinical picture Enlarged ends of long bones Wrists, knees Rickety rosary: costo-chondral junctions Harrisons sulcus Frontal bossing Bowing of legs: Localized – distal tibiae In sever cases: tetany, convulsions http://www.magazine.ayurvediccure.com/ www.thachers.org

Rickets – clinical picture Enlarged ends of long bones Wrists, knees Rickety rosary: costo-chondral junctions Harrisons sulcus Frontal bossing Bowing of legs: Localized – distal tibiae In sever cases: tetany, convulsions www.thachers.org

Rickets – clinical picture Enlarged ends of long bones Wrists, knees Rickety rosary: costo-chondral junctions Harrisons sulcus Frontal bossing Bowing of legs: Localized – distal tibiae In sever cases: tetany, convulsions www.thachers.org

Rickets – clinical picture Enlarged ends of long bones Wrists, knees Rickety rosary: costo-chondral junctions Harrisons sulcus Frontal bossing Bowing of legs: Localized – distal tibiae In sever cases: tetany, convulsions

Rickets – clinical picture Enlarged ends of long bones Wrists, knees Rickety rosary: costo-chondral junctions Harrisons sulcus Frontal bossing Bowing of legs: Localized – distal tibiae In sever cases: tetany, convulsions N Engl J Med 2009

Orthopedic Radiology, A Greenspan. lippincott Rickets – X-rays Widened physis (epiphyseal growth plate) metaphyseal end of physis Cupping of (weak new bone) Irregular Deformed bones Orthopedic Radiology, A Greenspan. lippincott

Orthopedic Radiology, A Greenspan. lippincott Rickets – X-rays Orthopedic Radiology, A Greenspan. lippincott

Orthopedic Radiology, A Greenspan. lippincott Rickets – X-rays Orthopedic Radiology, A Greenspan. lippincott

Rickets – lab results Serum Ca: Serum Phsphate: Alk Phosphatase: slightly low /or normal Serum Phsphate: Alk Phosphatase: High – a lot of bone turnover Vit. D level: low PTH level: Increased – scondary effect – to keep s. Ca level Urinary Ca: V. low

Rickets - treatment Vit. D and Calcium Most deformities correct gradually Sever deformities might need surgical correction

Hopophsphataemic rickets Vit. D resistant rickets Familial, X-linked Impaired renal tubular reabsorption of phosphate Lab. Results: Serum Phosphate: low Urinary phosphate: high Treatment: High dose Vit. D Phosphate

Orthopedic Radiology, A Greenspan. lippincott Osteomalacia Caused by defective Vit. D: Deficiency – lack of sun exposure Intestinal malabsorption Defective formation of active Vit. D: Liver or Renal disease Clinical features Bone aches – backache, hip pain Compressed vertebral fracture Insufficiency fractures of femur / tibia Orthopedic Radiology, A Greenspan. lippincott

Apley’s System of Prthop & Fractures Osteomalacia – X-rays Weak osteopaenic bone Biconcave vertebrae & compression fractures Trefoil pelvis – acetabular protrusion Typically: Looser’s zones: Poorly healing stress fractures Neck of scapula Neck of femur Pubic bones Apley’s System of Prthop & Fractures

Apley’s System of Prthop & Fractures Osteomalacia – X-rays Weak osteopaenic bone Biconcave vertebrae & compression fractures Trefoil pelvis – acetabular protrusion Typically: Looser’s zones: Poorly healing stress fractures Neck of scapula Neck of femur Pubic bones Apley’s System of Prthop & Fractures

Orthopedic Radiology, A Greenspan. lippincott Osteomalacia – X-rays Weak osteopaenic bone Biconcave vertebrae & compression fractures Trefoil pelvis – acetabular protrusion Typically: Looser’s zones: Poorly healing stress fractures Neck of scapula Neck of femur Pubic bones Orthopedic Radiology, A Greenspan. lippincott

Apley’s System of Prthop & Fractures Osteomalacia – X-rays Weak osteopaenic bone Biconcave vertebrae & compression fractures Trefoil pelvis – acetabular protrusion Typically: Looser’s zones: Poorly healing stress fractures Neck of scapula Neck of femur Pubic bones http://www.omjournal.org Apley’s System of Prthop & Fractures

Orthopedic Radiology, A Greenspan. lippincott Osteomalacia – X-rays Looser’s zone Orthopedic Radiology, A Greenspan. lippincott

Hyperparathyroidism Primary: Secondary: Tertiary: Parathyroid adenoma / hyperplasis Secondary: Hyperplasia due to hypocalcaemia Tertiary: Autonomous activity after secondary hyperplasis

Orthopedic Radiology, A Greenspan. lippincott Hyperparathyroidism Effect of PTH Target organs: Kidneys Bones Intestines (indirect) Bone weakens, resorption Increased serum Ca Orthopedic Radiology, A Greenspan. lippincott

Hyperparathyroidism Bones Stones Moans Groans Rarefaction Subperiosteal resorption (middle phalanges) Reorption of lateral end clavicle Brown tumors Stones Kidney stones and nephroclacinosis Moans Abdominal pain, renal pain Groans Pschological depression, stress

Hyperparathyroidism – x-rays Bones Rarefaction Bone resorption Subperiosteal resotption middle phalanges Tibial shaft lateral end clavicle Brown tumors Skull: salt & pepper Soft tissue calcification www.eurorad.org

Hyperparathyroidism – x-rays Bones Rarefaction Bone resorption Subperiosteal resotption middle phalanges Tibial shaft lateral end clavicle Brown tumors Skull: salt & pepper Soft tissue calcification Orthopedic Radiology, A Greenspan. lippincott

Hyperparathyroidism – x-rays Subperiosteal bone resorption Orthopedic Radiology, A Greenspan. lippincott

Hyperparathyroidism – x-rays Bones Rarefaction Bone resorption Subperiosteal resotption middle phalanges Tibial shaft lateral end clavicle Brown tumors Skull: salt & pepper Soft tissue calcification Orthopedic Radiology, A Greenspan. lippincott

Hyperparathyroidism – x-rays Subperiosteal bone resorption Orthopedic Radiology, A Greenspan. lippincott

Hyperparathyroidism – x-rays Bones Rarefaction Bone resorption Subperiosteal resotption middle phalanges Tibial shaft lateral end clavicle Brown tumors Skull: salt & pepper Soft tissue calcification Orthopedic Radiology, A Greenspan. lippincott

Hyperparathyroidism – x-rays Bones Rarefaction Bone resorption Subperiosteal resotption middle phalanges Tibial shaft lateral end clavicle Brown tumors Skull: salt & pepper Soft tissue calcification Orthopedic Radiology, A Greenspan. lippincott

Hyperparathyroidism – x-rays Bones Rarefaction Bone resorption Subperiosteal resotption middle phalanges Tibial shaft lateral end clavicle Brown tumors Skull: salt & pepper Soft tissue calcification http://www.radpod.org/2008

Hyperparathyroidism – x-rays Bones Rarefaction Bone resorption Subperiosteal resotption middle phalanges Tibial shaft lateral end clavicle Brown tumors Skull: salt & pepper Soft tissue calcification Orthopedic Radiology, A Greenspan. lippincott

Hyperparathyroidism – x-rays Bones Rarefaction Bone resorption Subperiosteal resotption middle phalanges Tibial shaft lateral end clavicle Brown tumors Skull: salt & pepper Soft tissue calcification Orthopedic Radiology, A Greenspan. lippincott

Hyperparathyroidism - treatment Hydration Reduced calcium intake If adenoma: Surgical removal Beware of the “hungry bone” syndrome post operatively – severe hypocalcaemia (why?)

Scurvy – Vit. C deficiency First discovered in sailors Failure of collagen fibers formation Weak osteoid matrix Clinical picture: Child irritable, anemia Bleeding gums Pain and swellings at ends of long bones

Scurvy – Vit. C deficiency X-rays: Osteopaenia – more at mataphysis Sub-periosteal bleeding Periosseous calcification Ring epiphysis Sclerosis at juxtaepiphyseal metphysis Treatment: Vit C (large doses)

Scurvy – Vit. C deficiency Orthopedic Radiology, A Greenspan. lippincott

Scurvy – Vit. C deficiency Orthopedic Radiology, A Greenspan. lippincott

Scurvy – Vit. C deficiency X-rays: Osteopaenia – more at mataphysis Sub-periosteal bleeding Periosseous calcification Ring epiphysis Sclerosis at juxtaepiphyseal metphysis Treatment: Vit C (large doses)

Summary Bone is an active tissue Calcium is an important mineral Continuous absorption and rebuilding Calcium is an important mineral Calcium control Diseases Osteoporosis Rickets and Osteomalacia Hyperparathyroidism Scurvy