12.10 Metabolic Bone Diseases Flashcards
Different bone cells that provide metabolic activity
- osteoblasts (4-5%) – make new bone (build)
- osteoclasts (1-2%) – resorb old bone (chew)
- osteocytes (90-95%) – “mechano-sensing” & regulatory functions
Intracellular signalling
- mevalonate pathway and bone
➡️ prenylation (addition of hydrophobic molecules to protein - RANK (receptor activator of nuclear kappa beta) – ligand
➡️bind to RANK receptor on OC (osteoclasts)
➡️ produced by osteoblasts
➡️promotes osteoclastogenesis (enhance bone resorption)
➡️ regulator: OPG (osteoprotegerin) - osteoprotegerin
➡️block RANK-ligand RANK interaction
➡️ produced by osteoblasts and osteocytes
➡️may thus decrease osteoclastogenesis (protects against bone resorption) - sclerostin
➡️inhibit bone formation
➡️ produced by osteocytes
Define metabolic bone disease
Broad umbrella term for wide spectrum of diseases associated with disturbance of normal bone remodeling, bone metabolism and bone integrity.
Define osteoporosis
Metabolic bone disease characterized by:
- decreased bone strength (⬇️ ability of skeleton to withstand trauma)
- with increased bone fragility
- susceptibility to fracture due to a decrease in the amount of normally mineralized bone
- a decrease in micro-architectural integrity.
- ⬇️ quantity of bone
High risk category pt for developing osteoporosis
Normal physiology of ageing - highest risk category
- older postmenopausal female (≥ 65 yrs) and the elderly male (≥ 70 yrs) based on physiology per se
➡️ lower peak bone mineral density in women compared to men
➡️increased bone resorption at menopause in women (accelerated bone loss at menopause)
➡️decreased bone formation and bone quality with ageing in both genders
External (contributing) factors
- adult patients with significant clinical risk factors or a secondary cause of excessive bone loss.
Two main categories of contributors to low bone mass & skeletal fragility
1. clinical risk factor (CRF)
- contributor to bone loss that is not a specific disease or a bone unfriendly pharmacological agent and may be non-modifiable or modifiable
2. secondary causes
- specific systemic disease or bone toxic medication responsible for adverse bone effects
Non-modifiable clinical risk factors for low bone mass & skeletal fragility
- age: (fracture risk 2-5 fold higher in elderly than in the young)
- genetics: parental history of hip fracture (maternal) - is a largely BMD independent RF for all fractures
-
gender and ethnicity: OP and fractures occur more frequently in women than men as previously noted with marked ethnic variation and in SA highest in Indian and white populations
previous low trauma fracture: very important risk factor for subsequent fracture, best defined in age groups 40-50 yrs and older, risk is highest within 12 months after injury and dependent on site involved
Modifiable clinical RF for low bone mass and skeletal fragility
- excessive leanness (BMI 22-18kg/m2): lean vs fat mass, mechanical, hormones
- excess alcohol (> 3U daily): direct toxin, nutrition, gonadal, cortisol, falls
- smoking: low weight, low estrogen, early menopause, nutrition
- nutritional risk factors: low calcium intake, hypovitaminosis D, protein-energy malnutrition – restrictive diets
- hypogonadism: use of progesterone contraceptives, athletes amenorhoea, delayed puberty (also regarded as specific disease / secondary cause if premature ovarian failure)
Secondary causes of low bone mass and skeletal fragility
- Long-term glucocorticoid therapy
- Alcoholism
- Hypogonadism including hormone deprivation Px
- Rheumatoid arthritis
- Chronic lung diseases
- Inflammatory GI disorders
- Hypercalciuria
- Renal failure
- Cancers (myeloma…..)
- Medication (other)
- HIV and HIV treatment
Osteomalacia
- in adulthood mostly associated with phosphate or severe vitamin D deficiency
- state of decreased mineralization or softening of bone
- normal unmineralized quantity of organic bone matrix
- DXA-BMD measurement low in these patients due to suboptimal mineralization
- to consider in patient who presents with bone and muscle pain, marked proximal muscle weakness and skeletal fragility
- renal phosphate loss consequence of some of ARV regimens
- distinguish from OP via clinical features, biochemical findings and unique radiological findings
Paget’s disease
- sclerotic bone disease, cause focal abnormalities in the skeleton that may be unifocal or multicentric and often affect pelvis, skull and long bones
- only focal sclerotic bone disease that cause bony expansion (enlargement)
- thought to be due to a slow viral infection in genetically susceptible person with distortion of normal bone remodeling
- may present with pain, deformity and even fracture in the affected area
- serum ALP high in active disease and best marker of disease
- consider if focal sclerosis of skeleton noted on radiology, certain malignancies cause sclerotic bone metastases and can be distinguished from Paget’s on basis of bony enlargement
