Case Study Osteoporosis

10 October 2016

Thus, over time, there is loss of total bone volume. While everyone experiences slow, gradual loss in bone volume after age 30, those with osteoporosis have accelerated loss. 4. Describe the microscopic features of osseous tissue that normally help long bones withstand lateral stress without breaking. A lateral stress placed on a bone (e. g. on Margaret’s right femur) actually causes (A) compression of the bone on the side of impact and (B) stretching (tearing) on the side opposite of the impact. Mid-way through the bone, these “compressive” and tearing” forces cancel each other out, and thus tough, compact bone is not needed in the middle. Instead, this middle area (or “medullary cavity”) is filled with yellow and red bone marrow. The outer rim (or “bony collar”) is what experiences the greatest stress on lateral impact. It withstands this stress in the following ways: (A)

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On the side of impact, the bony collar withstands compressive crushing by virtue of the tough hydroxyapatite crystals in its extracellular matrix. Arranged in concentric layers within the osteons (Haversian systems) of compact bone, these hydroxyapatite crystals serve as weight-bearing pillars for the bone. B) On the side opposite of the impact, the bony collar withstands tearing apart by virtue of the vertically arranged bundles of tough collagen in the extracellular matrix of bone. This collagen is oriented in a spiraling vertical pattern in which the fibers in each concentric lamella are roughly perpendicular to those in adjacent lamellae (i. e. a “plywood-like” design). 5. Describe the microscopic features of osseous tissue that normally help long bones withstand compressive stress without breaking. Surgeons performed an open reduction of Margaret’s fracture, immobilizing the bones with internal pins.

The bony collar of long bones helps them withstand compressive stress by the mechanism described in #4A above (i. e. hydroxyapatite, weight-bearing pillars). In addition, long bones also withstand compressive forces by virtue of the spongy (“cancellous”) bone in the epiphyses. The interlocking network of bony plates (called “trabeculae”) found in spongy bone help to distribute the weight of the body out to the tough bony collar of the diaphysis. In this way, bony plates act much like the trusses or struts in old-time railroad bridges which distribute the weight of the train evenly over the entire bridge.

Given the above considerations, Margaret’s osteoporotic femurs are vulnerable to fracture because of (A) the loss of spongy bone in the epiphyses and (B) the thinning of the bony collar in the diaphysis. 6. Describe the changes that a broken bone undergoes as it is healing. Steps in repair: A. fracture hematoma (i. e. blood clot) forms B. soft tissue callus(1st 3 to 4 weeks)| – fibroblasts and osteoblasts migrate in from the periosteum and endosteum- fibroblasts lay down a collagen matrix – some of the fibroblasts differentiate into chondroblasts (i. e. cartilage-forming cells) and lay down a fibrocartilage splint (i. e. oft tissue callus)| C. bony callus(starting 3 to 4 weeksafter the injury)| – osteoblasts begin to replace the fibrocartilage splint with spongy and compact bone, forming a bulge that is initially wider than the original bony shaft| D. bone remodeling| – as the patient starts to use (or bear weight on) the bone, the bone starts to remodel along lines of maximal stress (this remodeling process requires the activity of both osteoblasts and osteoclasts| 7. During her long recovery, Margaret is advised by her physician to begin weight-bearing as soon as she can. How does weight-bearing influence the process you described in question #6? Be specific in your answer and describe what weight-bearing does to bone at the microscopic level. ) The most popular hypothesis regarding the effect of weight-bearing on bone remodeling is called Wolff’s law . Wolff’s law states that bone grows and remodels in response to the mechanical stresses placed upon it (e. g. from muscle pull or gravitational pull). Thus, bone is laid down along lines of maximal stress. This is presumably why: A. long bones are the thickest midway down the diaphysis, where the stresses are the greatest. B. curved bones are the thickest where they are most likely to buckle (e. . note the thick greater trochanter of the proximal femur). C. the bony plates in spongy bone are oriented like weight-bearing trusses. D. large bony processes are located where muscles attach to (and pull on) bone. When Margaret begins to bear weight on her right femur, she is introducing a lateral stress in the direction shown below: Physiological measurements reveal that placing stress on a bone generates a negative electrical charge on the compressed surfaces of the bone and a positive electrical charge on the stretched surfaces of the bone (see above drawing).

Furthermore, studies have shown that negatively charged bony surfaces prevent parathyroid hormone (PTH) from stimulating bone resorption by osteoclasts. Thus, bone builds up in these areas. Conversely, bone resorption occurs on positively charged bony surfaces. Therefore, when Margaret begins to bear weight on her right femur, she is stimulating new bone formation on the medial side of her proximal femur and bone resorption on the lateral side of her femur. The net result of this remodeling process is the formation of a bone that is ideally designed for the stresses that it will most likely encounter.

This is why physicians encourage weight-bearing as soon as possible during the bone-healing process. 8. Aside from any effect on the healing process, why else might Margaret’s physician want her to avoid a prolonged period of bed-ridden inactivity? Extended bed rest can have detrimental effects on an individual, especially if that individual is elderly. Prolonged bedrest increases one’s risk of developing bedsores, respiratory infections, thrombophlebitis with possible pulmonary embolism as a complication, and further loss of bone volume (i. e. exacerbating Margaret’s already present osteoporosis).

This last point, in fact, is an excellent illustration of the other side of Wolff’s law — i. e. bone is reabsorbed where it is no longer needed. Prolonged bed rest and immobility means less daily stress placed upon the skeleton. Over time, bone mass will be lost. This is seen in astronauts who spend several weeks in space — the loss of gravity means that less stress is placed on the weight-bearing bones. Upon their return to earth, these astronauts are found to have notable loss in bone volume. 9. What risk factors does Margaret have for osteoporosis? Margaret has several risk factors for osteoporosis: A.

She is elderly. (Osteoporosis is more common in the elderly, particularly postmenopausal women. ) B. She is a cigarette smoker. C. She is Caucasian. (Osteoporosis is more common in Caucasians than in individuals of other races. ) D. She is sedentary. (This lack of exercise means that she is placing less stress on her skeleton — see discussion of Wolff’s law in question #7. ) Other potential risk factors for osteoporosis include: A. estrogen depletion (the primary reason why postmenopausal women are commonly affected) B. decreased bone mass at the end of development C. testosterone depletion D. alcohol abuse E. alcium deficiency (especially a problem in the elderly because of decreased intestinal absorption of calcium). 10. What parts of the skeleton (i. e. what bones) are most vulnerable to the ravages of osteoporosis? The loss in bone volume due to osteoporosis is seen throughout the skeleton, affecting spongy bone slightly more than it affects compact bone. This loss in bone volume places bones at risk for fracture. The most common site of fracture is in the lower thoracic and upper lumbar vertebrae. Fractures here are typically compression fractures which may occur slowly and gradually over time, or occur suddenly.

The gradual compression of the anterior portion of the vertebral bodies in the cervical and thoracic vertebrae give rise to the kyphosis deformity (“humpback”) of osteoporosis. Another common place for a fracture is in the distal radius, as the victim of osteoporosis attempts to break his/her fall by reaching out with the hands. The proximal femur is another common site of fracture (as occurred in Margaret). These hip fractures occur primarily in individuals over 75 and are associated with substantial morbidity and mortality (for reasons discussed in #8 above).

Hip fractures are almost always associated with a fall, but it is not always clear whether the fracture precedes or follows the fall. Osteoporosis affects over 20 million Americans. In addition, over 1. 5 million people over age 45 suffer from osteoporosis-related fractures annually, most common of which are fractures of the hip, vertebrae, and limb bones The medical cost of treating patients with osteoporosis and osteoporotic fractures was estimated in 1990 to exceed $10 billion annually. This number will rise as the baby boomers age. 11.

Following her recovery, Margaret was placed on three medications: (A) oral calcium supplementation,(B) oral estrogen, and (C) oral alendronate sodium (Fosamax). Specifically describe how each of these medications works to treat Margaret’s condition. (A) oral calcium supplementation – Calcium provides an important raw material for bone formation. (B) oral estrogen – Studies clearly show that estrogen deficiency can accelerate osteoporosis, but the mechanism for the protective effect of estrogen is not clear. Estrogen may stimulate osteoblasts to lay down new bone (estrogen receptors have recently been found on osteoblasts). C) oral alendronate sodium (Fosamax) – This drug inhibits the bone resorbing capabilities of osteoclasts. 12. Other treatments for osteoporosis include (A) sodium fluoride and (B) calcitonin. Describe how each of these medications works to treat osteoporosis. (A) sodium fluoride – Sodium fluoride specifically stimulates new bone formation by activating osteoblasts. (B) calcitonin – Calcitonin is a natural peptide hormone secreted by C-cells in the thyroid gland. Calcitonin is an inhibitor of osteoclasts, and thus slows down bone resorption. It also increases vitamin D production and absorption of calcium in the small intestine.

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