Upload
suzanna-carson
View
216
Download
0
Embed Size (px)
DESCRIPTION
3 Mature bone consists of: 1. Mineral component – hydroxyapatite (Ca10(PO4)6)OH)2 (calcium and phosphate)
Citation preview
Metabolic bone diseases
K. Bernášková
2
Bone functions
• Body shape and movement• Protection of cavities• Acid – base ballance• Erythropoesis, immunity
• Calcium homeostasis• Regulation of glucose metabolism
3
Mature bone consists of:
1. Mineral component
– hydroxyapatite (Ca10(PO4)6)OH)2 (calcium and phosphate)
4
Regulation of calcium homeostasisPTH Calcitriol Calcitonin Cortizol
Calcemia Bone resorption
Ca2+ reabsorption in the kidneys
(+
phosphates)
_ _
Ca2+ resorption in the gut
Indirectly
(+ phosphates
) _
Mutual influences
Activates the conversion of vitamin D inthe kidneys
level decreases PTH concentration (directly and indirectly)
PTH effect on the bone PTH
secretion, calcitriol effect in the gut
5
Mature bone consists of:
1. Mineral component
2. Organic matrix (osteoid) – collagen fibers (type 1)– osteocalcin– protein S – proteoglycans, glycoproteins
9
Mature bone consists of:
1. Mineral component
3. Bone cells– osteoblasts– osteocytes– osteoclasts
2. Organic matrix (osteoid)
10
Osteoblasts• Derived from mesenchymal stem
cells of the bone marrow stroma
• Function: bone matrix production, bone mineralisation, control of osteoclasts maturation and function
• Rich in alkaline phosphatase• Have receptors for PTH, vitamin D, growth factors, estrogen;mechanoreceptors
11
Osteocytes
• Derived from osteoblasts
• Trapped in formed bone
• Function: Calcium homeostasis, bone nutrition (?), help in bone remodelation process (sensor of bone load)
12
Osteoclasts
• Derived from hemopoeticstem cells (monocyto-makrofage series)
• Maturation and function is controlled by osteoblasts• Receptors for calcitonin• Function: bone resorption, changes of blood calcium concentration
13
Osteoclast
14
Structure of a long bone
15
Bone remodeling
• Continuous processContinuous process
• 2 types: 2 types: targeted targeted (started by microingury, (started by microingury, ccycle lasts for 4 months)stochasticstochastic (whole skeleton) (whole skeleton)
• Resorption and formation should be in ballanceResorption and formation should be in ballance
16
Bone remodeling cycle
17
Importance of bone remodeling
• Maintenance of calcium and phosphate Maintenance of calcium and phosphate homeostasishomeostasis
• Maintenance of structural integrity of Maintenance of structural integrity of the bone - reparation of small the bone - reparation of small injuries (microtrauma)injuries (microtrauma)
• Adaptation of shape and bone Adaptation of shape and bone organisation to changes in organisation to changes in biomechanical forcesbiomechanical forces
18
Regulation of the remodeling process
calcaemia and phosphataemia mechanical forces body metabolism hormones local factors
by
19
Bone remodeling regulation 1• Systemic regulation Resorptio
nFormation
PTH ()calcitriol ()calcitonin 0cortizol
STH () ()T3, T4 ()estrogen androgen
()
()
insulin 0
20
Bone remodeling regulation 2• Local factors Resorptio
nFormation
Cytokines
PRG E2
Factors from osteoblasts
, ()
Growth factors
()
21
Metabolic bone diseases= due to imbalance between bone resorption and formation
= characterized by abnormal structure of the entire bony skeleton, increased fragility and pain
may reflect disturbances in the mineral phase, organic matrix, the cellular processes of remodeling and the endocrine, nutritional and other factors may be hereditary or acquired
22
Types of metabolic bone diseases
1.1. OsteoporosisOsteoporosis2.2. OsteomalaciaOsteomalacia3.3. Osteitis fibrosa cysticaOsteitis fibrosa cystica4.4. Paget‘s diseasePaget‘s disease5.5. Renal osteopathyRenal osteopathy6.6. OsteopetrosisOsteopetrosis
23
1. Osteoporosisis a systemic bone disease characterized by
decreased bone density, resulting in thinning and increased porosity of the bone
• bone resorption predominates (of both organic bone resorption predominates (of both organic and mineral components)and mineral components)
• the trabecular (spongiform) bone is affected the trabecular (spongiform) bone is affected moremore
• epidemiologically significant occurrence !epidemiologically significant occurrence !
• fragility of the bones increases (increases fragility of the bones increases (increases propensity to fractures)propensity to fractures)
24
Osteoporotic changes in vertebrae
25
The development of osteoporosis depends on:
– Colour of skin – Sex– Basal bone density (peak bone mass)– Activity (sports)– Nutrition, body weight (smoking)– Calcium and phosphate intake – Vitamin D presence– Estrogen and androgen level– Family history
26
Types of osteoporosis• primary
» juvenile»postmenopausal ( estrogen bone resorption bone resorption plasmatic plasmatic
Ca2+ Ca2+ PTH PTH activation of vit D to activation of vit D to kalcitriol kalcitriol Ca2+ resorption from the gut) Ca2+ resorption from the gut)
»senile ( kalcitriol - kalcitriol - Ca2+ resorption from GIT Ca2+ resorption from GIT PTH PTH
bone resorption) bone resorption)
• secondary (many causes)
27
Causes of secondary osteoporosis
Endocrine Hypogonadism ThyreotoxikosisHyperparathyreosisCushing‘s syndrome
Connective tissue diseases Osteogenesis imperfecta Marfan‘s syndrome Ehlers-Danlos‘s syndrome
MalignanciesMyeloma
Leukemia
LymfomaOsteolytiOsteolytic metastases
Other causesGastrointestinal disordersChronic kidney disease Immobilization
Diet
Drugs glucocorticoids, alcohol, warfarine, (antiepileptics)
28
Signs and symptoms of osteoporosis
Osteopenia on RTG Compressing fractures and wedging of the
vertebrae Kyphotic deformity of the spine Pain Fractures of the femoral neck and distal radius
(Colles‘)
29
Osteoporosis
30
Osteoporosis
26- year-old manSubstituted by cortisol for a long time (hypopituitarism)
31
Therapy of osteoporosis• Prevention!
• Estrogen; selective modulators of estrogen receptors in bones (tamoxifen); (androgen)
• Calcium• Vitamin D• Bisfosfonates (fosamax)• Sodium fluorid • PTH, calcitonin, (leptin) • Vitamin K
Resorption
Formation
PTH ()calcitriol ()calcitonin
0
cortizol
STH () ()T3, T4 ()estrogen androgen
()
()
insulin 0
32
2. Osteomalatia/rickets• Due to invalide
mineralisation of bone (late or missing)
• in children called ricketts (seraph disease)
• not so rare as affirmed
33
Pathophysiology of osteomalatia
vitamin D hypocalcaemia PTH calcaemia , but phosphataemia
calcium – phosphate disproportion doesn‘t allow normal mineralisation
wide osteoid border, decreased bone formation
• changes in both spongiform and compact bone
34
Causes of osteomalatia • vitamin D deficit
(diet; malabsorption; disorders of vitamin D metabolism in skin, liver or kidneys; receptor disease)
• phosphate deficit disorder of phosphate reuptake in kidneys (phosphate diabetes, Fanconi‘s sy)
• deficit of alcalic phosphatase in osteoblasts• toxic substances
(fluorid, aluminium, antacid‘s binding phospate)
35
Signs and symptoms of osteomalatia
• diffuse bone pain (predominantly hip region) • muscle weakness• fractures due to minimal forces• biochemistry:
hypocalcaemia, hypophosphataemia, slightly PTH
• in children growth retardation, bone deformities
36
Signs of ricketts
37
Ricketts
Deformation of long bones
Enlarged epiphysis at wrist
38
Ricketts
39
Rickets
• tetany, convulsions• failure to thrive• apathy
40
3. Osteitis fibrosa cystica
= complication of advanced hyperparathyreosis (very rare recently)
= extensive activity of osteoclasts bone resorption and fibrous replacement,
fibrous degeneration of bone marrow, cystic or tumor-like lesions (brown tumours)
• Softened bones of the entire skeleton deformations
41
Osteitis fibrosa cystica
42
Osteitis fibrosa cystica
43
4. Paget‘s disease
• the second most common metabolic bone disease
• bone cells increase their volume, number and activity
• local damage
• metabolic turnover of bone increases up to 40x
= osteitis deformans
44
4. Paget‘s disease (osteitis deformans)
• Cause unknown (viruses?)
• Abnormal activity of osteoclasts bizarre and irregular pattern of resorption
• Increased osteoblastic response irregular bone formation
So called „Woven bone“
45
Sign‘s, symptoms and complications of Paget‘s disease
Signs and symptoms: often asymptomatic; pain, fracture, warmth feeling
Complications: Bone deformation (bowing long bones, deformation of hip, „growing“ of the head) Nerve compression palsies ( deafness, weakness and paresthesias in lower extremities) Fractures Left heart failure (rare) Neoplastic transformation of affected bone
46
Paget‘sdisease
- bowing long bones
47
Paget‘s disease
Massy (1513): Portrait of an old woman
48
5. Renal osteopathy
• Bone damage due to chronic renal failure
• Multifactorial
• Combination of osteoporosis, osteosclerosis, osteomalatia, osteitis fibrosa
49
Renal osteopathy
Aluminium toxicity
amount of nephrons
biosyntethic activity
calcitriol formation
Ca and P resorption in GIT
kidney excretory functions
Retention of toxic metabolits
Metabolic acidosis
phosphataemia
calcaemia
PTH secretion
Osteitis fibrosa
Remodeling of bone Osteosclerosis
Metastatic calcifications
Calcium –phosphate disbalance(bone -buffer)
Osteoporosis
Protein-caloric malnutrition
Growth disturbance in children
bone senzitivity to calcitriol
Osteomalatia
Drugs
50
6. Osteopetrosis
• Rare hereditary disease• Heterogenous
pathophysiology ( quantity or activity of osteoclasts)
• Bone resorption failure thickening of bones x incresed fragility
• Dg RTG skull changes: „Alien“
51
Thank you for your attention
52
Literature:
• http://depts.washington.edu/bonebio/ASBMRed/diseases.html
53
Calcium – phosphate relationships phosphate + calcium primary hyperparathyreosis
PTHrp
+ N calcium Phosphaturia Secondary hyperparathyreosis in vitamin D deficiency
+ calcium D hypovitaminosis Vitamin D receptor insensitivity
phosphate + calcium Terciary or quartery hyperparathyreosis in failing kidneys Vitamin D excess Sarcoidosis Increased bone resorption (myeloma, lymphoma, bone metastases, bone tumours)
+ N calcium Increased phosphate intake (laxatives) Transiently in secondary hyperparathyreosis due to kidney failure
+ calcium Decreased PTH Phosphate retention in chronic kidney failure + metastatic calcification