metabolic bone disorders

Prof. Mamoun KremliAlMaarefa College

Metabolic Bone Disorders

Objectives

• Bone as an active tissue

• Calcium is an important mineral

• Calcium metabolism – 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++

Bone components

A: Matrix:

• Organic: (40% of dry weight)• Collagen fibers

• Cells

• Inorganic (Minerals): (60%)• Ca++ hydroxyapatite, Ca++ phosphate

• Others

B: Cells:• Osteoblasts, osteoclasts, osteocytes, others

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

• Growth:• Epiphyseal:

• Endochondral ossification

• On surface:• Oppositional

ossification

Miller Review of Orthopaedics

Bone growth & remodeling

• In Adults:• Remodeling 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

Bone Regulation


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)

BM

D,

g/c

m2

Age (yrs)

TOTAL BODY FEMORAL NECK LUMBAR SPINE

Change in BMD (mean ± 1SD) with age in healthy male (--) and female (--)(DPX, Lunar)

Body Calcium

• Most of Calcium in body is present in bone• Release of Calcium 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)

• Calcium serum levels have to be controlled quickly

• Renal reabsorption • Intestinal absorption

Causes of Calcium absorption

• intake of phosphates (as in soft drinks)

• intake of oxalates (as in tea and coffee)

• Drugs: corticosteroids

• Intestinal ma-labsorption syndromes

Players in Ca regulation

• Vit. D is the general crude regulator• Target organs:

• Small intestines

• Bones

• PTH is the sensitive fine regulator• Target organs:

• Kidneys (v. quick)

• Bones (slow)

• (indirectly): small intestine


• Cacitonin: C cells of Thyroid• Opposite PTH on bone and kidneys

• Good to bone

• Oestrogen:• Protects bone from PTH

• Good to bone


• Corticosteroids:• Bad to bone

• Reduce osteoblastic activity, and increases osteoclastic activity

• Reduce calcium absorption from intestine, and increase renal excretion of calcium

• Local – BMP (Bone Morphogenic Proteins)

• Mechanical stress:• Strengthens bone

Calcium metabolism

http://www.google.com.sa/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=R103CHVWVmBSYM&tbnid=hbCOkisbVR50JM:&ved=0CAUQjRw&url=http://images.rheumatology.org/viewphoto.php?albumId=75677&imageId=2861766&ei=754AU4m_KuKM0AXC_ICACg&psig=AFQjCNGHei192PICxdAAxN1mKGFHxIe6cg&ust=1392635981102878

Hormonal regulation of Ca met.

Hormonal regulation of Ca met.

Mesutti, 2011

Laboratory investigations

• X-rays

• Bone mineral density (BMD)• DEXA scans: Dual Energy Xray Absorptiometry

• Biochemical tests:• Serum Ca, Phosphate

• Serum Alkaline 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• 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• 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





• Neck of femur


http://library.med.utah.edu


www.rcuv.org/tag/health





• Neck of femur


http://library.med.utah.edu

Orthopedic Radiology, A Greenspan. lippincottApley’s System of Prthop & Fractures





• Neck of femur


• Loss of cortical thickness• seen on X-rays


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 (estrogen):

• 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

Nutritional Calcium Deficiency

Miller Review of Orthopedics

Rickets - pathology

• Matrix forms, not calcified

• In growing physis• Widened physis (epiphyseal growth plate)

• Cupping of metaphyseal end (weak new bone)

• Irregular metaphyseal end


Rickets - pathology

• Matrix forms, not calcified

• In growing physis• Widened physis (epiphyseal growth plate)

• Cupping of metaphyseal end (weak new bone)

• Irregular metapyseal end

• 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

• Harrison’s sulcus

• Frontal bossing

• Bowing of legs:• Localized – distal tibiae

• In sever cases: tetany, convulsions





• Harrisons sulcus

• Frontal bossing



http://www.magazine.ayurvediccure.com/

www.thachers.org





• Frontal bossing



www.thachers.org





• Frontal bossing







• Frontal bossing



N Engl J Med 2009

Rickets – X-rays

• Widened physis (epiphyseal growth plate)

• metaphyseal end of physis• Cupping of (weak new bone)

• Irregular

• Deformed bones


Rickets – X-rays


Rickets – lab results

• Serum Ca:• slightly low /or normal

• Serum Phsphate:• slightly low /or normal

• 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

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


Osteomalacia – X-rays

• Weak osteopenic bone

• Biconcave vertebrae & compression fractures

• Trefoil pelvis – acetabular protrusion

• Typically: Looser’s zones:• Poorly healing stress fractures

• Neck of scapula

• Neck of femur

• Pubic bonesApley’s System of Prthop & Fractures






• Neck of scapula

• Neck of femur

• Pubic bones

Apley’s System of Prthop & Fractures






• Neck of scapula

• Neck of femur

• Pubic bones







• Neck of scapula

• Neck of femur

• Pubic bonesApley’s System of Prthop & Fractures

http://www.omjournal.org


• Looser’s zone


Osteomalacia - Treatment

• Treat the cause• Vit. D

• Calcium

• Sun exposure

Hyperparathyroidism

• Primary:• Parathyroid adenoma / hyperplasia

• Secondary:• Hyperplasia due to hypocalcaemia

• Tertiary:• Autonomous activity after secondary

hyperplasia

Hyperparathyroidism

• Effect of PTH• Target organs:

• Kidneys

• Bones

• Intestines (indirect)

• Bone weakens, resorption

• Increased serum Ca


Hyperparathyroidism

• Bones• Rarefaction

• Subperiosteal resorption (middle phalanges)

• Reorption of lateral end of clavicle

• Brown tumors

• Stones• Kidney stones and nephroclacinosis

• Moans• Abdominal pain, renal pain

• Groans• Pschological: depression, stress

Hyperparathyroidism – x-rays


• Bone resorption• Subperiosteal resorption

• middle phalanges

• Tibial shaft

• lateral end clavicle

• Brown tumors

• Skull: salt & pepper

• Soft tissue calcification

www.eurorad.org



• Bone resorption• Subperiosteal resotption


• Tibial shaft


• Brown tumors


• Soft tissue calcificationOrthopedic Radiology, A Greenspan. lippincott


• Subperiosteal bone resorption






• Tibial shaft


• Brown tumors





• Subperiosteal bone resorption






• Tibial shaft


• Brown tumors


• Soft tissue calcification Orthopedic Radiology, A Greenspan. lippincott





• Tibial shaft


• Brown tumors








• Tibial shaft


• Brown tumors



http://www.radpod.org/2008





• Tibial shaft


• Brown tumors


• Soft tissue calcificationOrthopedic Radiology, A Greenspan.

lippincott





• Tibial shaft


• Brown tumors


• Soft tissue calcificationOrthopedic 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


• X-rays:• Osteopenia – more at metaphysis

• Sub-periosteal bleeding• Peri-osseous calcification

• Ring epiphysis

• Sclerosis at juxta-epiphyseal metaphysis

• Treatment:

• Vit. C (large doses)

Summary

• Bone is an active tissue• Continuous absorption and rebuilding

• Calcium is an important mineral

• Calcium control• Vit. D, PTH, Calcitonin, Steroids, estrogen, mechanical

stress, …

• Diseases• Osteoporosis

• Rickets and Osteomalacia

• Hyperparathyroidism

• Scurvy

metabolic bone disorders

Documents

cancellousold bone

slow loss of bone mass

remodeling of existing

ca regulationcacitonin

ca regulationcorticosteroids

ca phosphateothersb

ca regulationvit

strongerannual bone