Fahim Khan

Bone

Short Answer Questions: Answer 2/3 or all 3 for extra credit.1. A postmenopausal woman slips while stepping off a curb, falls, andcracks her pelvic bone. During diagnosis, the physician begins toconsider the possibility of osteoporosis. What are the symptoms and riskfactors of osteoporosis? What diagnostic procedures would the physicianorder to verify the diagnosis of osteoporosis? If the diagnosis isverified, what treatment will the physician initiate?2. Describe how calcium homeostasis is regulated by calcitriol,calcitonin and parathyroid hormone.3. Compare the structure and functions of spongy and compact bone.Compare the mechanisms of intramembranous ossification and endochondrialossification.

1. Osteoporosis causes bone to become abnormally porous (collagen and calcium islost) and this decrease in mass and density makes the bone weaker than normal. The boneeasily fractures or, in areas like the spine, may compress (leading to a hump or scoliosis).There aren’t really any symptoms, other than something overt like a bone fracture, butthere are several well-defined risk factors.For example, osteoporosis commonly affects postmenopausal women because thefemale body stops producing estrogen, since the menstrual cycle ceases as ovaries stopreleasing eggs; estrogen production is directly related with calcium absorption in bones.Most women who get osteoporosis are either white or Asian, and usually over 70 sincethe process of bone loss is gradual and doesn’t manifest as a serious problem until around30% of bone mass loss at age 70 – and, in fact, the longer you live the worse your bonesget (also, entering menopause earlier means more bone damage due to estrogendeprivation occurring earlier). Not only elderly white/Asian women get osteoporosis though, as other risk factorsfor it include long periods of inactivity due to injury (or laziness), smoking, eatingdisorders, certain medications e.g. anticonvulsants, overconsumption of alcohol, toomuch protein in diet, too little calcium in diet, and lack of sunlight (required for the bodyto make vitamin D, which itself aids in calcium absorption).A physician could verify that a person has osteoporosis by performing a bonedensity scan (usually

dual-energy X-ray absorptiometry or DEXA, with low absorptionmeaning low density; other options are ultrasound, or normal X-rays)

. A blood or urinetest for chemical markers that may point to occurrence of bone formation also works.Treatments for osteoporosis involves avoiding its preventable risk factors(exercise, end smoking/alcohol/coffee addiction, get enough calcium and vitamin D).Also, estrogen hormone replacement therapy (HRT) for menopausal women,

selectiveestrogen receptor modulator (SERM) therapy (similar to HRT therapy without increasedrisk of breast cancer, though it may increase chances of dangerous blood clots),biophosphinates that slow down bone destruction rate, calcitonin to increase boneturnover rate (so that bones don’t have a chance to become brittle), calcitriol (a vitamin-D

replacement used against postmenopausal osteoporosis), or teriparatides to promote boneformation.

2. Calcitriol is activated vitamin D and its role is to increase calcium absorption bystimulating intestines, and decrease calcium and phosphate excretion (reduces urinarysecretion). It also promotes osteoclast activity, which results in destruction of bone. Allthree processes of course increase blood calcium concentration.Calcitonin (secreted by C cells in thyroid) reduces calcium when there is toomuch by quickly (in 15 minutes) reducing osteoclast activity by up to 70%, andincreasing osteoblast number and acitivity. The osteoblasts create new bone,incorporating calcium into their structure.Parathyroid hormone (PTH) secreted by parathyroid glands increases bloodcalcium level by promoting osteoclast production and activity, while reducing osteoblast bone formation, reducing calcium secretion and increasing phosphate secretion (whichcontrols bone destruction) in urine. PTH also plays a crucial part in the formation of calcitriol.The interaction of these three hormones prevent hypercalcemia and hypocalcemia.3. Compact bones are solid bones that sandwich spongy bones (AKA diploe) – because of this, compact bones are divided into inner and outer varieties (inner sidefacing a body cavity). Spongy bones are mostly hollow, with crisscrossing struts calledtrabeculae that are spread throughout for strength. The hollow structure of spongy boneallows them to act as “shock absorbers” that dissipates damage to the outer compact boneso that the inner compact bone isn’t damaged (which would probably result in woundingvital organs and also open up the body to the outside). Compact and spongy bones arefound in flat bones, such as those found in the sternum or cranium.The two types of bone formation – intramembranous (IM here for convenience)and endochondrial (EC, for convenience) ossification – correspond to different bonetypes. IM ossification results in flat bones, while EC ossification results in mostly long bones.IM ossification starts out with the mesenchyme – undifferentiated progenitor cellsthat are part of the embryonic mesoderm – “congealing” into strands (since the IC matrixis gel-like) into the precursors of spongy bone – a network of trabeculae. Osteoblastsform uncalcified osteoid tissue on the trabeculae, and then calcium phosphate crystallizesthe structured matrix formed, with some of the osteoblasts getting trapped within and becoming osteocytes. Osteoblasts on the surface form compact bone while osteoclasts inthe network carve out hollow marrow spaces.EC ossification means bone forming within cartilage. The bone sort of grows out,so that by looking at a piece of long bone, the diaphysis would be the origin of growthwhile the epiphyses are the latest growths. The diaphysis was originally cartilage(chondrocytes) which became ossification centers (first steps in making bone), and theouter membrane (the perichondrium) produce a bony collar. This new structure preventsdiffusion of nutrients into inside so chondrocytes inside die and the resulting hollowspace becomes the marrow or medullary cavity. A periosteal bud forms around the bonycollar and produces osteogenic cells that go into the marrow and become osteoblasts, andthese start depositing osteoid tissue which calcify into trabeculae (not unlike IM