Bone has an obvious mechanical function as well as it serves an equally imp role as a mineral reservoir.
Bone is in continuous state of flux i.e. its internal shape and structure changing from moment to moment in concert with normal variation in mechanical function and mineral exchange.
Alterations in mineral ion conc. Regulates hormones and local factors Controls cellular Activity Modulates bone structure and composition The metabolic bone disorders are conditions in which generalized skeletal abnormalities result from disruption of the complex interactive system
Collagen fibres are arranged parallel to each other to form multiple layers with osteocytes in between
It is laid only on existing bone surface
It occurs in two structurally different forms :
Cortical : made up of compact units – haversion system( osteons) These compact units consist of haversion canals having blood vessels, lymphatics and nerves and surrounded by concentric lamellae of bone with the osteocytes lying in between.
Cancellous bone – present in internal meshwork of all bones, ends of tubular bones, vertebral bodies.
It has a honeycomb appearance, the structural units comprising of flattened sheets that can be thought of as unfolded osteons. These units are arranged according to the mechanical needs of the structure i.e. thickest and strongest along trajectories of compressive stress and thinnest in plane of tensile stress
The spaces between the trabeculae are the opened out vascular spaces containing the marrow and fine sinusoidal vessels
This comprises only 1/4 th of the bone mass but 2/3 rd of the bone surface area.
It is covered with marrow and that’s why the effect of metabolic disorders are first seen here.
Osteoblast : concerned with bone formation, derived from mesenchymal precursors & from row of cells along free surface of trabeculae.
These are rich in alk phosphatase and responsible for prod of type I collagen
At the end of bone remodelling cycle they either remain on newly formed surface as lining cell or enveloped in matrix as resting osteocyte.
Osteocyte : spent osteoblast, communicate with each other with cytoplasmic process. They are sensitive to mechanical stimuli & communicate information about changes in stress and strain to active osteoblast.
under the influence of PTH they participate in bone resorption and Ca ion transport
Osteoclast : principle mediators of bone resorption.
Derived from monocyte precursors in marrow ( osteblast and T lymphocyte express RANK ligand that on chemotactic stimuli bind to RANKL receptors on monocyte and release M-CSF & convert monocyte to osteoclast. Osteoprotegrin is competitve inhibitor of this process )
By chemotactic stimuli they come and attach to specific regions on cell surface – ruffled border and release lysozyme.
with the resorption of organic matrix osteclast come and left in shallow excavations called Howship lacunae
Puberty to 30 yrs : haversion canal and intertrabecular spaces are filled in & cortices increase in overall thickness – bones become heavier and stronger.
bone mass is increased 3% every yr and attains peak bone mass in 3 rd decade ( affected by genetic, hormonal, dietary, environmental factors) the greater the peak bone mass the less will be the effect of inevtible depletion of bone.
>30yrs : slow inexorable loss of bone starts i.e. haversion space enlarge, trabeculae becomes thinner, endosteal surface resorbed, medullary space expands.
Bone loss occurs at the rate of 0.3% per yr in men & 0.5%per yr in women
After menopause in women : phase of rapid bone loss
3% per yr for the next 10 yrs predominantly in trabecular bone
this is as a result of increased osteoclastic activity due to loss of inhibition of gonadal hormones
60 – 75 yrs : rate of bone loss decreases and becomes steady at 0.5% ( this phase is due to decreased osteoblastic activity
BMD, g/cm 2 Age TOTAL BODY Change in BMD (mean ± 1SD) with age in healthy male ( -- ) and female ( -- )
Fn of Ca : coagulopathy, nerve fn, contraction of muscle.
Ca in bone occurs in two forms : readily exchangeable (500mmol/day) and slowly exchangeable (7.5mmol/day) which is more stable form and concerned with bone remodelling by constant resorption & deposition
A large amount of Ca is filtered in kidneys & 98-99% is reabsorbed ( 60% in prox tubule and rest in ascending limb of loop of henle and regulated in turn by PTH)
Ca absorbed from the GI tract is actively transported out of the intestine by system in brush border involving Ca dependent ATPase and regulated by 1,25-DHCC. Some absorption also occurs by passive diffusion.
When Ca intake is high – 1,25-DHCC level falls and increase with deficient Ca intake.
Defective bone growth results from retardation of normal epiphyseal cartilage growth and calcification. Cartilage cells fail to complete their normal cycle of proliferation and degeneration, with subsequent failure of capillary penetration and it occurs in patchy manner, result is frayed irregular epiphyseal line at the end of shaft. Failure of osseous and cartilage matrix to mineralize in the zone of preparatory calcification, followed by newly formed uncalcified osteoid results in wide irregular frayed zone of nonrigid tissue (the rachitic metaphysis)
Normally the epiphyseal line of long bone is well defined narrow strip of cartilage(2mm deep) is widened in rickets because the cartilage zone is hyperplastic but the normal palisade arrangement of cells is lost.
Mineralization is also defective in subperiosteal bone, preexisting cortical bone is resorbed in normal manner, but replaced by unmineralized osteoid and the shaft loses rigidity casing distortion and fractures.
With healing the degeneration of cartilage cell along the diaphyseal metaphyseal border occurs, capillary penetration in resultant spaces is resumed and calcification in the zone of prep calcification takes place producing a line visible on radiographs.
The clinical picture consists of rickets with severe hypocalcemia and alopecia, although a variant without alopecia exists. Patients without alopecia appear to respond better to treatment with vitamin D metabolite
Genetic mutations in calcitriol receptor ( D dependent rickets type 2)
Biochemistry vitD normal; 25(OH)D normal; 1,25 (OH) 2 D high; Ca low; PTH high; Alk Ph high; P low
Both autosomal recessive and autosomal dominant (FGF 23) inheritance have been found and have been associated with the same clinical phenotype. In approximately one third of patients, the disease appears to occur as a consequence of a new mutation. Clinical findings are similar to those of nutritional rickets, but without proximal myopathy.
Because calcium levels remain normal, neither tetany nor secondary hyperparathyroidism are present.
Kidneys fail to excrete phosphate – phosphate rise in blood – excess phosphate excreted into gut – phosphorus combines with Ca in gut – Ca level falls – PTH released – ca withdrawn from bone – rickety changes.
Osteodystrophy (ie, renal rickets) is the only variety of rickets with a high serum phosphate level. It can be adynamic (a reduction in osteoblastic activity) or hyperdynamic (increased bone turnover).