5. Increase in Bone Mass with Age in Children
The changes seen in bone mass in children is due, almost entirely, to bone growth or modeling. The amount of bone in the skeleton increases probably into our 200s with the majority deposited in the skeleton during the 3 year interval around peak growth velocity.
Peak bone mass is major determinant of bone density at all stages of adult life for this reason it is sometimes referred to as a pediatric disease with geriatric consequences.
When you see kids in adolescence, they still have the capacity to do something to influence the conditions of their bones when they are fully grown. We, however, generally see people who are on the far side of the slippery slope who can do nothings about peak bone mass and are dealing with the consequences years later.
The changes seen in bone mass in children is due, almost entirely, to bone growth or modeling. The amount of bone in the skeleton increases probably into our 200s with the majority deposited in the skeleton during the 3 year interval around peak growth velocity.
Peak bone mass is major determinant of bone density at all stages of adult life for this reason it is sometimes referred to as a pediatric disease with geriatric consequences.
When you see kids in adolescence, they still have the capacity to do something to influence the conditions of their bones when they are fully grown. We, however, generally see people who are on the far side of the slippery slope who can do nothings about peak bone mass and are dealing with the consequences years later.
7. Osteoclast
Most important aspect of bone physiology to understanding how osteoporosis develops and how our treatments work is bone remodeling, illustrated on this slide.
One new BMU every 6 secs;
In most circumstance, two processes are tightly coupled
Most important aspect of bone physiology to understanding how osteoporosis develops and how our treatments work is bone remodeling, illustrated on this slide.
One new BMU every 6 secs;
In most circumstance, two processes are tightly coupled
8. Bone Remodeling Process
The bone remodeling process begins when the cells lining the bone surface are activated to form osteoclasts.
Osteoclasts secrete acid, which dissolves the bone mineral, to form resorption cavities (pits).
Osteoblasts are recruited to the resorbed bone and secrete osteoid matrix, which is comprised mainly of collagen.
Over time, the osteoid matrix becomes mineralized to form bone.
The bone remodeling process begins when the cells lining the bone surface are activated to form osteoclasts.
Osteoclasts secrete acid, which dissolves the bone mineral, to form resorption cavities (pits).
Osteoblasts are recruited to the resorbed bone and secrete osteoid matrix, which is comprised mainly of collagen.
Over time, the osteoid matrix becomes mineralized to form bone.
9. slide 9
With PHPT, excessive turnover bad- not enough time for mineralization
But need turnover to repair microdamage, make sure bone is strong for mech loading
With PHPT, excessive turnover bad- not enough time for mineralization
But need turnover to repair microdamage, make sure bone is strong for mech loading
12. High Bone Turnover Leads to Development of Stress Risers and Perforations
Note that stress risers are NOT microfractures or microcracks. Stress risers are only points of critical mechanical compromise in the bone structure, at which the application of a significant mechanical stress (strain, torsion, etc) makes this area as very susceptible to sustaining a fracture.
Note that stress risers are NOT microfractures or microcracks. Stress risers are only points of critical mechanical compromise in the bone structure, at which the application of a significant mechanical stress (strain, torsion, etc) makes this area as very susceptible to sustaining a fracture.
14. Biochemical Markers of Bone Turnover Released During Remodeling Process
During the process of bone remodeling, enzymes and proteins produced by the cells involved in remodeling or the breakdown products of the bone tissue itself are released into the circulation and some eventually make it into the urine. These biochemical markers, which reflect ( but do not control) the rate of bone remodeling have provided a great deal of insight into the pathogenesis of osteoporosis and the mechanisms by which our therapeutic agents work. Although we will refer to these later on when we discuss therapy, they are not generally recommended for the clinical management of osteoporosis.
During the process of bone remodeling, enzymes and proteins produced by the cells involved in remodeling or the breakdown products of the bone tissue itself are released into the circulation and some eventually make it into the urine. These biochemical markers, which reflect ( but do not control) the rate of bone remodeling have provided a great deal of insight into the pathogenesis of osteoporosis and the mechanisms by which our therapeutic agents work. Although we will refer to these later on when we discuss therapy, they are not generally recommended for the clinical management of osteoporosis.
17. 10
Bone loss accelerates in older ages most likely related to physiologic and nutritional changes that result in worsening calcium and vitamin D deficiencies.
Bone loss accelerates in older ages most likely related to physiologic and nutritional changes that result in worsening calcium and vitamin D deficiencies.
18. Blood Ca++
Major purpose of these 2 slides is to illustrate the necessity of good calcium and D intake by pointing out the obligate calcium loses daily in urine (~10,000 mg/day filtered- 98-99% reabsorbed) and GI secretions ; if enough calcium coming into the GI tract from diet or supplements and there is adequate vitamin D to help absorb it there is enough to replace the loses and keep serum calcium normal.
Major purpose of these 2 slides is to illustrate the necessity of good calcium and D intake by pointing out the obligate calcium loses daily in urine (~10,000 mg/day filtered- 98-99% reabsorbed) and GI secretions ; if enough calcium coming into the GI tract from diet or supplements and there is adequate vitamin D to help absorb it there is enough to replace the loses and keep serum calcium normal.
19. Blood Ca++
However, if there is inadequate calcium intake or absorption (as in this slide) there is a net loss of calcium from the body and the physiologic defenses are activated to preserve a normal serum calcium ..review increased PTH and its actions on urinary calcium (unable to stop calcium losses entirely), activation of vitamin D and increase in bone remodeling .
If this situation is chronic, there is obligate bone loss
Make point why serum calcium tells us nothing about the adequacy of calcium intake.
Will be coming back to this over and over again in the case discussions because it is critical to bone health and both Rx and prevention of osteoporosis
However, if there is inadequate calcium intake or absorption (as in this slide) there is a net loss of calcium from the body and the physiologic defenses are activated to preserve a normal serum calcium ..review increased PTH and its actions on urinary calcium (unable to stop calcium losses entirely), activation of vitamin D and increase in bone remodeling .
If this situation is chronic, there is obligate bone loss
Make point why serum calcium tells us nothing about the adequacy of calcium intake.
Will be coming back to this over and over again in the case discussions because it is critical to bone health and both Rx and prevention of osteoporosis
20. Mean calcium intake
Source: National Health and Nutrition Examination Survey (NHANES)
Intake in girls 9-19 has decreased by 100 mg/day between NHANES II and III
Source: National Health and Nutrition Examination Survey (NHANES)
Intake in girls 9-19 has decreased by 100 mg/day between NHANES II and III
21. 0
Combination of sex-steroid deficiency, inadequate calcium and vitamin D nutrition and aging invariably leads to bone loss at all anatomical site and, with bone loss, a rise in the rate of fractures
Combination of sex-steroid deficiency, inadequate calcium and vitamin D nutrition and aging invariably leads to bone loss at all anatomical site and, with bone loss, a rise in the rate of fractures
22. Adapted from Meunier PJ, et al. Clin Ther. 1999;21:1025-1044
Exponential rise in fractures as bone density increases indicates that bone density is a major determinate of bone strength and fracture risk. In fact, many in vivo and in vitro studies suggest that BMD account for 60-80% of the strength of bone. Butt..
Exponential rise in fractures as bone density increases indicates that bone density is a major determinate of bone strength and fracture risk. In fact, many in vivo and in vitro studies suggest that BMD account for 60-80% of the strength of bone. Butt..
24. Relationship Between BMD and
ANIMATED SLIDE
In untreated individuals, each 1 SD reduction is BMD is associated with a 2-fold increase in risk of fracture.
If the reverse were true in response to treatment, a 1 SD increase in BMD would result in a 50% decrease in fracture risk.
The next slide shows that this is not the case.
ANIMATED SLIDE
In untreated individuals, each 1 SD reduction is BMD is associated with a 2-fold increase in risk of fracture.
If the reverse were true in response to treatment, a 1 SD increase in BMD would result in a 50% decrease in fracture risk.
The next slide shows that this is not the case.
26. T= - 2 Z= - 0.5
Graph by courtesy of S. Petak:
Graphic representation of T and Z-scores.
Can be ungrouped to illustrate various points and then re-grouped to move and size.
Example: 60-year-old woman with a T-score = 2 and Z-score= 0.5.
Graph by courtesy of S. Petak:
Graphic representation of T and Z-scores.
Can be ungrouped to illustrate various points and then re-grouped to move and size.
Example: 60-year-old woman with a T-score = 2 and Z-score= 0.5.
29. Relationship Between BMD and
ANIMATED SLIDE
In untreated individuals, each 1 SD reduction is BMD is associated with a 2-fold increase in risk of fracture.
If the reverse were true in response to treatment, a 1 SD increase in BMD would result in a 50% decrease in fracture risk.
The next slide shows that this is not the case.
ANIMATED SLIDE
In untreated individuals, each 1 SD reduction is BMD is associated with a 2-fold increase in risk of fracture.
If the reverse were true in response to treatment, a 1 SD increase in BMD would result in a 50% decrease in fracture risk.
The next slide shows that this is not the case.
32. Relative Influence of Inner and Outer Diameters on Bone Strength
This figure illustrates the impact of changing the Moment of Inertia on bone strength. Starting from the initial state (A), a moderate degree of endosteal resorption (expansion of the marrow space by 3 units) is balanced by application of 1 unit to the periosteal surface, resulting in no change in bending strength.
Lee CA, Einhorn TA. The Bone Organ System, Form and Function. In Marcus R, Feldman D, Kelsey J, Eds. Osteoporosis, 2nd Edition. Academic Press, San Diego, 2001 Volume 1, pp. 3-20.
This figure illustrates the impact of changing the Moment of Inertia on bone strength. Starting from the initial state (A), a moderate degree of endosteal resorption (expansion of the marrow space by 3 units) is balanced by application of 1 unit to the periosteal surface, resulting in no change in bending strength.
Lee CA, Einhorn TA. The Bone Organ System, Form and Function. In Marcus R, Feldman D, Kelsey J, Eds. Osteoporosis, 2nd Edition. Academic Press, San Diego, 2001 Volume 1, pp. 3-20.
33. Relevance of Architecture to Structural Strength
This figure illustrates the loss of bone strength due to trabecular thinning (loss of quantity) and perforation of trabeculae (loss of architecture). The strength of a trabecular strut is proportional to the square of its radius. Preservation of architecture is essential for bone strength.
This figure illustrates the loss of bone strength due to trabecular thinning (loss of quantity) and perforation of trabeculae (loss of architecture). The strength of a trabecular strut is proportional to the square of its radius. Preservation of architecture is essential for bone strength.
36. hip axis length
Shape of bones are also important to their susceptibility to fracture in ways that we donnt clearly understand use Asians as example 50% lower risk of hip fracture at same levels of BMD. Mention that some of protection of AA from hip fracture also due to shorter hip axis length. not yet part of our clinical armamentarium for fracture perdition, it may be someday.
Shape of bones are also important to their susceptibility to fracture in ways that we donnt clearly understand use Asians as example 50% lower risk of hip fracture at same levels of BMD. Mention that some of protection of AA from hip fracture also due to shorter hip axis length. not yet part of our clinical armamentarium for fracture perdition, it may be someday.
38. Contributors to strength
Trabecular thickness
Trabecular number
Connectivity
Matrix quality/mineralization
Emphasize connectivity
Accelerated and unbalanced turnover can undermine all of these
Emphasize connectivity
Accelerated and unbalanced turnover can undermine all of these
39. Excess resorption leads to trabecular thinning
May also lead to trabecular perforation and loss of connectivity
Loss of horizontal struts disproportionally reduces strength of cancellous bone (a 10% bone loss which interrupts connectivity reduces strength by 70%)1
When resorption is increased and exceeds formation two consequences thinning of trabeculae and trabecular perforations
10% bone loss due to trabecular thinning reduces strength by 20%
10% bone loss which causes loss of connectivity leads to a 70% loss of strength.
When resorption is increased and exceeds formation two consequences thinning of trabeculae and trabecular perforations
10% bone loss due to trabecular thinning reduces strength by 20%
10% bone loss which causes loss of connectivity leads to a 70% loss of strength.
40. Changes in trabecular architecture with age
It is just this pattern of bone loss which occurs with aging and sex-steroid deficiency. Make point that rapid bone loss is particularly dangerous in this regard as it increases the risk for trabecular perforations
It is just this pattern of bone loss which occurs with aging and sex-steroid deficiency. Make point that rapid bone loss is particularly dangerous in this regard as it increases the risk for trabecular perforations
43. Adapted from National Osteoporosis Foundation, Physicianns Guide to Prevention and Treatment of Osteoporosis.
Modified from Riggs BL and Melton LJ III. Osteoporosis: Etiology, Diagnosis, and Management. New York: Raven Press; 1988
Review pathophysiology mention falling
Review pathophysiology mention falling
44. Adapted from National Osteoporosis Foundation, Physicianns Guide to Prevention and Treatment of Osteoporosis.
Modified from Riggs BL and Melton LJ III. Osteoporosis: Etiology, Diagnosis, and Management. New York: Raven Press; 1988
Knowing what you now know about bone physiology you will now be able to understand how our therapeutic agents work
Talk though effects of anti-resorptives and PTH on bone quality as well as on bone remodeling balance. Mention importance of fall prevention- all of which we will be talking about more over the next day and a half.
Knowing what you now know about bone physiology you will now be able to understand how our therapeutic agents work
Talk though effects of anti-resorptives and PTH on bone quality as well as on bone remodeling balance. Mention importance of fall prevention- all of which we will be talking about more over the next day and a half.