Compare compact bone to trabecular
compact has haversian system with osteons and circumfirential lamellae
trabecular: has spicuateled
•80-90% of volume is calcified
•Fulfills mainly a mechanical and protective function
•15-25% of volume is calcified
•Fulfills mainly a metabolic function •~20% of bone
Cortical and trabecular bone are constituted of the same cells and the same matrix elements, but there are ______ differences.
structural and functional
Where does most of the bone breakdown happen? whats the timeline for this process?
in trabecular bone
2 weeks to breakdown, months to rebuild
Explain process of bone remodeling
Have osteoclasts lead teh way followed by blasts laying out new bone behind them
12 BRUs activated each minute, with annual turnover rate of 25%. l High turnover rate because of
the higher surface-tovolume ratio; accounts for 80% of turnover
3 BRUs activated each minute, with annual turnover rate of 2-3%.
l Lower turnover rate; accounts for 20% of turnover
l Less vascularity
Osteoid laid down in discrete layers, 3µm thick
l Lamellae deposited in curved sheets that follow the contour of the trabeculae
buidling of trabecular bone
Osteoblasts plus blood vessels follow osteoclasts through hollowed-out tunnel
l Concentric lamellae laid down
Cortical bone growth
what is the heirarchical structure in bone?
collagen moleculre (type I) --> collagen fibril--> fibers--> lacuna--> haversian canal
the heirarchical structure of bones supplies them with what characteristics?
stiff, strong, tough and ductilie
resist damage, can be bent but also resist it and can bend before it bbreaks
What is the role of cement lines in bone?
both parallel and perpendicular
the perpendicular are better at resisting fracture
Why do we say that bone has dual physiology?
• Mechanical physiology – Loading – Unloading
• Mineral balance physiology – Ca balance – Phosphate balance
A skeletal disorder characterized by
– Compromised bone strength predisposing to
– An increased risk of fracture
WHO Definition of Osteoporosis
Bone strength reflects the integration of two main features:
– Bone density (easily measured)
– Bone quality (not as easily measured with presently available tools)
Long bones are slightly curved and are loaded primarily by_____
• There is tension on 1 side of the bone and compression on the other
• Vertebrae are loaded primarily in ____and ____
compression and torsion
•Past vertebral deformity is_____ predictive of future vertebral fracture than a 1 SD change in spinal BMD
•Past vertebral deformity is_____ predictive of hip fracture as a 1 SD change in spinal BMD
•These risks are_____ of age and BMD
What can we see on histology of bone with osteomalacia?
see lots of osteoid and unmineralized shit
Medications to ts osteoporosis
The interfaces between lamellae, and between osteons are called ______ and can absorb and dissipate force while preventing a crack from passing from one lamella to its neighbor.
While osteoporosisis a recognized clinical diagnosis, conceptually it is problematic. People do not suffer from low bone mineral density (BMD) unless they suffer____. Whether fractures occur depends on many factors in addition to BMD. For these reasons, it is more correct to consider osteoporosis as a risk factor for fracture, j
dual energy X-ray absorptiometry (DXA).A T-score ___ in a postmenopausal woman or a man over 50 is defined by the World Health Organization as the densitometric criterion for osteoporosis
A key difference between osteomalacia and osteoporosis is that in the latter, the quantity of _____is insufficient and its architecture is impaired
In adults, osteod volume is normally under 5% of the bone surface, but in osteomalacia, the osteoid surface is increased, sometimes dramatically so. PTH is typically elevated, as mineral deficiency drives
The bone isoform of ______ (tissue non-specific alkaline phosphatase, encoded by the TNSALP gene) and_____ (N-terminal propeptide of type 1 collagen) are typically elevated, as osteoblasts are working properly and secrete all their usual products.
Antiresorptives work by limiting the initiation of new bone remodeling units to tx osteoporosis ,why does this work?
Since bone formation takes longer than bone resorption, inhibiting the process of remodeling at its inception allows the remodeling space to be filled.
For simple nutritional deficiency leading to osteomalacia, what can we do to tx pts?
improving diet or giving supplements to provide sufficient vitamin D and Ca is sufficient therapy.
It is important to note that the elemental Ca content of supplements varies, based on the molecular weight of the anion.
CaCO3 is___% elemental Ca
while Ca citrate is only___% elemental Ca.
tamoxifen, raloxifene are both examples of
Estrogens and Selective Estrogen Receptor Modulators (SERMs, e.g.
h estrogens and SERMs can prevent the increased remodeling
these work by inhibiting conversion of mevalonate to farnesyl, interfering with protein modification in osteoclasts, ultimately leading to apoptosis.
These two bisphosphotanes cause esophageal irritation.
Two most potent bisphosphanates
pamidronate, zoledronic acid
Bisphosphatates are sooo cool and be used for:
In addition to their use in preventing fragility fractures, bisphosphonates are used in Paget’s disease, osteogenesis imperfecta, and to prevent bone metastases in certain cancers.
What are my 4 bisphosphates
pamidronate, zoledronic acid
is an injected decoy receptor for RANKL. When RANKL binds to the drug, it is unable to bind to its endogenous receptor RANK, and interruption of RANKL-RANK signaling prevents osteoclast differentiation.
is safe for patients with impaired renal function, but it also can cause ONJ and atypical femoral fractures. It has been associated with an increased susceptibility to skin infections and can also cause nausea, weakness, and fatigue.
is normally produced by the C-cells of the thyroid and acts to lower serum Ca levels. One of its actions is to suppress osteoclast activity following binding to specific receptors on their surface. C
can lead to dramatic increases in bone mass.
is an anabolic
best given episodically
is the storage form of vitamin D, and its level is used to assess the adequacy of body stores
25-OH vitamin D
vitamin D is fat soluble and 25-OH vitamin D stores are
relatively stable (half-life ~1 week).
.Vitamin D undergoes 1-hydroxylation in the____ to yield 1, 25 di-OH vitamin D, the biologically active form.
1, 25 di-OH vitamin D has direct effects on the intestinal epithelium to____ Ca and phosphate absorption and on bone to____ remodeling
Chronic negative Ca balance leads to ______ and, if sufficiently prolonged, may lead to osteomalacia.
Serum Ca falls, stimulating____, which acts to increase dietary Ca and phosphate absorption and to release Ca and phosphate from bone mineral.
Note that there are many paths to secondary hyperparathyroidism: the most important are
nutritional deficiency, renal disease leading to impaired vitamin D activation, GI disease leading to malabsorption, and use of medications that accelerate vitamin D clearance, such as anti-epilectic drugs
Mutations of _____ (encoded by CYP27B1), the vitamin D receptor (encoded by VDR) occur in vitamin D resistant rickets, or the hormone response element binding protein, which prevent VDR from binding to its target sites in the genome. T
Phosphate is abundant in most diets, so the body’s challenge is usually not how to maintain adequate serum and tissue levels, but how to clear it. The kidneys actively excrete phosphate under the regulation of
PTH and fibroblast growth factor 23 (FGF23).
is believed to be a key regulator of phosphate homeostasis, acting as a phosphaturic hormone
In addition to promoting phosphaturia, FGF23 inhibits expression of ______, thereby reducing vitamin D activation.
It increases activity of ________, increasing vitamin D clearance. By lowering phosphate through urinary losses, FGF23 decreases PTH secretion.
Tumor induced osteomalacai, Autosomal dominant hypophosphatemic rickes, autosomal recessive hypohsphatemic rickes and xlinke rickets are all
All hypophosphatemic disordres included elevated levels of
FGF23, hypophosphatemia adn osteomalacia
Patients may complain of bone pain and may have bone tenderness on deep palpation of the tibia or other long bones. Low trauma fractures, especially stress fractures, are common. Fractures may heal poorly
Sign of Osteomalacia
result of abnormal bone modeling when osteomalacia is present prior to the closure of the epiphyses.
What type of bone do we see in pt with Pagets?
Impaired biomechanical performance. Normal bone is lamellar in structure, but when remodeling is very rapid, newly formed bone is woven and lacks the interfaces between layers that contribute to bone’s toughness.
What is characteristic of vascular supply in Pagets?
Increased vascularity of the lesion: Pagetic lesions are often hypervascular, and if located near the surface of a bone, warmth from increased blood flow may be present.
Bone deformity is seen in Pagets: Both bowing due to abnormal modeling and dysregulated remodeling can occur. This feature of Paget’s disease leads to its other name—
What do we see on histology in pagets?
woven bone pattern
Skull disease in Pagets can often causes headache, can cause an increase in hat size, and may lead to deafness due to impingement on the 8th cranial nerve. Other nerve impingement syndromes may also occur
Pagetic lesions have an increased risk of malignant transformation, and____ occurs in about 1% of patients, a rate much greater than that of the general population.
How do we Dx Pagets?
Diagnosis is most often made on the basis of symptoms, characteristic radiographic findings, marked elevation of alkaline phosphatase (marker of osteoblastic activity), and a positive bone scan (also dependent on osteoblastic activity).
Alkaline phosphatase is elevated in Pagets and is a maker for
increasted osteoblastic activity