Clinical Management of osteoporosis and other metabolic bone diseases Flashcards
3 main functions of bone
Reservoir of calcium + phosphate
Haemopoiesis
- cancellous bone marrow supplies body with erythrocytes, leucocytes + platelets
Protective + mechanical
- Supports body’s tissues, protects soft internal viscera, provide sites of attachment for muscles that effect body movement and locomotion
2 types of bone structure
woven (immature)
lamellar (mature)
describe woven bone structure
Rapidly formed – collagen fibres aligned randomly and have no lamellae
Bone weaker but more flexible than lamellar bone
Found in embryonic and neonatal skeleton
Found in metaphyseal regions growing bones (up to age 4) and in fracture callus
describe lamellar bone structure
Forms the structural component of cortical and cancellous bone
Osteoblasts lay down collagen matrix in thin layered sheets (lamellae)
2 types of lamellar bone
cortical and cancellous
describe cortical lamellar bone
Mechanical and protective functions
80% adult skeleton
Found in diaphysis
Haversian system (osteon)
describe cancellous lamellar bone
Metabolic regulation of calcium
Found in metaphysis and epiphysis
No Haversian system - less strong than cortical bone
role of osteoblasts
baby bone cells
building blocks
Bone forming cells derived from undifferentiated mesenchymal stem cells in marrow
Produce osteoid (bone matrix) containing type 1 collagen
osteoclasts role
clean up cells
Found in marrow + circulating blood
Resorb bone
osteocyte role
cycle of bone
Osteoblasts that become entrapped by calcified bone matrix
90% bone cell population
Important in controlling calcium + phosphate
3 fates of osteoblasts
Become inactive bone lining cells
Surround themselves with matrix and become osteocytes
Disappear (apoptosis)
factors involved in bone remodelling
Vitamin D Nutrition Physical activity Age, hormones PTH IL1, TNF,TGF-β
why does bone remodelling occur
Allows bone to respond to loads (stresses)
Maintain materials properties
Allows repair of microdamage
Participates in serum Ca2+ regulation
what does bone remodelling involve
Cellular activation
Osteoblasts and osteoclasts are continuously recruited
Recruitment occurs at the “cutting” edge
Resorption
Osteoclasts active for ~12 days and then die
Causes release of IGF, FGF, etc., which recruits osteoblasts
Formation and Mineralization
Osteoid is formed by osteoblasts
Mineralization begins ~13 days later (1um/day)
Rate is same as osteoid formation
Mineralization continues after eroded volume filled in
what is ca important for
nerve, muscle, hormone function, clotting
absorption of calcium
Calcium absorbed from duodenum via active transport (regulated by 1,25-dihydroxycholecalciferol) and via passive diffusion from jejunum
2 roles of vit D in bone metabolism
Enhance calcium + phosphate absorption across small intestine
- Enhance osteoclastic resorption from bone
describe the activation process of vitamin D
UV light on skin transforms 7-dehydrocholesterol to cholecalciferol (vit D3)
Vit D3 subsequently hydroxylated in liver to inactive 25-hydroxycholecalciferol [25(OH)-Vitamin D3]
Further hydroxylation of 25-hydroxycholecalciferol in the kidney (PCT) to active 1,25-dihydroxycholecalciferol [1,25 (OH)2 vitamin D3]
what activates vitamin D
Activation in response to raised levels of PTH or decreased levels of serum calcium or phosphate
Decreased PTH levels or raised calcium or phosphate causes conversion of active form Vit D3 to inactive Vit D3
what cells secrete PTH
chief cells
what causes secretion of PTH
Secreted by chief cells of 4 parathyroid glands in response to extracellular calcium via calcium-sensing receptor
Secreted in response to decreased serum calcium + phosphate
what inhibits PTH release
Production inhibited by elevated serum calcium or (active) Vit D3
effects of PTH
Kidney
Stimulation of hydroxylation of 25(OH)-vitamin D3
Increasing reabsorption of filtered calcium in kidney
Promotes urinary excretion of phosphate from kidney
Bone
Stimulation osteoclasts and precursors–> bone resorption
OVERALL
Serum calcium levels increased
Phosphate levels decreased
what secretes calcitonin?
parafollicular C-cells of thyroid gland
what stimulates calcitonin release
elevated serum calcium
what inhibits calcitonin release
Inhibited by decreased serum calcium
effect of calcitonin
Directly inhibits osteoclasts (have calcitonin receptors) causing transient decrease in serum calcium
role of oestrogen in bone metabolism
Inhibits bone resorption (so prevents bone loss)
Also inhibits bone formation (so does not increase bone density)
what is osteoporosis
Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture
signs and symptoms of osteoporosis
Asymptomatic
Fragility fractures
Chronic pain
Deformity (kyphosis)
Impaired mobility
risk factors for osteoporosis
Non-modifiable Sex (female) Age Ethnicity Genetics Early menopause Small stature
(Potentially )Modifiable Alcohol Vit D deficiency Smoking Malnutrition Inactivity Heavy metals PPIs
Medical conditions Hypogonadal states Menopause, amenorrhoea, Turner syndrome… Endocrine disorders Cushing’s, ↑PTH, ↑T4, ↓T4 Malabsorption Coeliac, Crohn’s, UC, CF, short gut… Rheumatological conditions RA, Ank Spond, SLE… Renal insufficiency Haematological diseases MM, lymphoma, leukaemia… Inherited disorders Medications - Steroids, Phenytoin, Anticoagulants (warfarin, heparin) PPIs
pathophysiology of osteoporosis
Low peak bone mass Genetics (>20 genes) Oestrogen Environment factors Excessive bone resorption Inadequate bone formation
Bone formation < Bone resorption
diagnosis of osteoporosis
Bone Mineral Density (BMD)
The difference between your measurement and that of a young healthy adult is known as a T score
Thedifference between your measurement and that of someone of the same age is known as a Z score
N: T >-1.0
osteopenia -2.5
3 types of osteoporosis
1: postmenopausal- loss of trabecular bone
2: senile- loss of corticol and trabecular bone
3: secondary- loss of corticol and trabecular bone
mechanisms for falls
Intrinsic factors CVS Neuromuscular Visual acuity Locomotor Alcohol
Extrinsic factors
Lighting
Flooring
common fracture sites in osteoporosis
vertebra
hip
distal radius
clinical signs and symptoms of vertebral fractures
Signs
- Kyphosis
- Loss of height
- Tummy bulges due to loss of space under the ribs
Symptoms
- neck becomes weak and head falls forward
- pain in whole or part of back
- breathing difficulties
- indigestion and GORD
- stress incontinence
- difficulty with mobility
classification of osteoporosis
Primary
Post menopausal
Idiopathic osteoporosis in men
Osteoporosis in older people
Secondary
Disease e.g. rheumatoid arthritis, organ Tx
Iatrogenic e.g. steroids
Ix for osteoporosis
Full blood count Biochemistry Myeloma screen Gonadal function Vitamin D and PTH Bone density measurements
indications for referral for bone densitometry
Low trauma fracture (defined as a fracture which is either spontaneous or following a fall from the upright position)
Osteopenia or vertebral fractures on X-ray Steroid therapy Early menopause Secondary causes of osteoporosis Strong family history of osteoporosis
Mx of high risk osteopenia
Offer DEXA (rpt ~2 years) Bone-sparing drug tx if T-score
Mx for low risk osteopenia
Lifestyle advice, review <5 years
drugs for treatment of osteoporosis
Antiresorptive drugs
- Hormone replacement therapy
- Selective oestrogen receptor modulators
- Bisphosphonates
Bone formation drugs
-Teriparatide
Calcium & Vitamin D (All patients with osteoporosis)
define osteomalacia
‘A metabolic bone disease wheredefective mineralizationresults in alarge amount or unmineralized osteoid’
Qualitativedefect as opposed to a quantative defect like osteoporosis
Rickets and osteomalacia are manifestations of the same pathologic process
causes of nutritional osteomalacia
Vitamin D deficiency
- Lack of adequate sunlight
- Low intake of vitamin D
- GI diseases
Calcium deficiency
-Dietary
Phosphate deficiency
- TPN
- Chronic phosphate binder therapy
RFs for osteomalacia
vitamin-D deficient diets malabsorption e.g. celiac disease renal osteodystrophy hypophosphatemia chronic alcoholism tumors (tumor-induced osteomalacia) drugs
clinical features of osteomalacia
Bone pain Proximal weakness Symptoms from hypocalcaemia Deformity Fracture
Ix for osteomalacia
Low Ca Low Phosphate Low vitamin D Raised PTH X-ray / bone scan abnormalties Investigation for underlying abnormalities
Radiograph findings
Looser’s zones (insufficiency fractures)
medial femoral cortex
pubic ramus
scapula
fractures (especially in the proximal femur/femoral neck)
Bone scan: increased activity
treatment for osteomalacia
Underlying cause Eg coeliacs disease
Vitamin D supplements
- Oral Vitamin D3
- Oral 1,25 Vitamin D
- Intramuscular vitamin D3
what is Paget’s disease
A condition ofabnormal bone remodelling
excessivebone resorption and abnormal new bone formation
Disease of osteoclasts
Osteoclasts show abnormal morphology and are increased in number
Focal areas of increased and disorganised bone turnover
Focal bone is common
clinical features of Paget’s disease
Frequently asymptomatic Orthopaedic manifestations Pain (e.g. stress #, increased vascularity) Deformity Osteoarthritis Fracture Neurological symptoms Sarcomatous transformation less than 1% will develop malignantPaget's sarcoma(secondary sarcoma) Cardiac failure
Ix for Paget’s disease
Markers of bone turnover
- Alkaline phosphatase (serum)
- Collagen cross-link (urine)
X-rays -coarsened trabeculaewhich give the bone ablastic appearance -remodeled cortices -Long bone bowing
Isotope bone scans
Bone biopsy
Ddx for Paget’s disease
Raised alkaline phosphatase Metastatic bone disease Osteomalacia Hyperparathyroidism Liver disease
Similar radiographic appearance Metastatic disease Lymphoma Fibrous dysplasia Chronic osteomyelitis
Tx for Paget’s disease
Conservative
physiotherapy, NSAIDS, oral analgesics
Medical Bisphosphonates -Drugs which promote osteoclast apoptosis -Reduce bone turnover -Reduce woven bone formation -Increase lamellar bone formation -Improves bone strength
Surgical
E.g. arthroplasty
