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Please help me, I'm so scared!!?
Best answer:
could be a hernia. don't say it's a cystocoele when you go to a doctor. at your age, hernia is more common. Don't be too scared. But a doctor's appointment would really help relieving your worries. I can't recommend any non- medical treatment, though.I think this is what you have, and you need to go to another nurse, or your own doctor, right away. If they won't examine you, you need to be sure you can explain all the symptoms, and you should also let them know that you think it is the cystoceles. If one nurse turns you down, go to another. You need this looked at!!!dont worry go to a doctor and try to see what is wrong. it is important to go so please do. look, dont worry so much and it might turn out regular or somethingSweetie its ok to be scared,AND the nurse was/is a nut.You are never to young to "have"anything.Just go to the ER of see an OBGYN asap.Like Monday.IF your uterous perforates(sp)you could start heavy life threatening bleedingAlso your bladder could be damaged by simple neglect-not your neglect!.Everything inside is held together by muscle and tendon,they dont need to be overstreched.take care of YOU I'd like to have a wee chat with that "nurse".I'm actually angry.Just have a friend take you to ER okay. Write us back and lets us know your ok,please.Love and Prayers ,J
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Orignal From: Please help me, I'm so scared!!?
Sunday, July 8, 2012
Saturday, July 7, 2012
Tax Questions, Taxes etc. 2
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http://www.taxalmanac.org/index.php/Discussion:100%25_meal_deduction
There are certain instances where 100% deduction is allowed for M&E. Meals consumed on employer's premises for the convenience of the employer are 100% deductible (e.g., that pizza I ate at 8:00pm in my office during tax season). Meals that are billed out to client/customer and separately stated are 100% deductible to the biller and 50% deductible to the billee (e.g., travel expenses, including meals, that are billed out to the client as a reimbursable expense are 100% deductible, but the client may only deduct 50%).
As to deducting everyday lunches on Form 2106, meals are deductible when there is a business connection. When I go the Wendy's day after day, there is no business connection, and thus no deduction is allowed.
There are certain instances where 100% deduction is allowed for M&E. Meals consumed on employer's premises for the convenience of the employer are 100% deductible (e.g., that pizza I ate at 8:00pm in my office during tax season). Meals that are billed out to client/customer and separately stated are 100% deductible to the biller and 50% deductible to the billee (e.g., travel expenses, including meals, that are billed out to the client as a reimbursable expense are 100% deductible, but the client may only deduct 50%).
As to deducting everyday lunches on Form 2106, meals are deductible when there is a business connection. When I go the Wendy's day after day, there is no business connection, and thus no deduction is allowed.
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If the employees eat in an employer operated eating facility and the employees are provided meals for the convenience of the employer, the meal is an excludible fringe benefit under Sec. 132(e)(2) and the employer may deduct 100% of the meal costs under Sec. 274(n)(2)(B).
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Tax Questions Examples MEAL Deductions Cont.
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EXAMPLES::
JOHN D. MOSS, JR. and DIANE C. MOSS, Petitioners-Appellants,
EXAMPLES::
JOHN D. MOSS, JR. and DIANE C. MOSS, Petitioners-Appellants,
v.
COMMISSIONER OF INTERNAL REVENUE, Respondent-Appellee
UNITED STATES COURT OF APPEALS FOR THE SEVENTH CIRCUIT
No. 84-1820
January 17, 1985, Argued—March 27, 1985, Decided
Lead opinion by POSNER
211 POSNER, Circuit Judge. The taxpayers, a lawyer named Moss and his wife, appeal from a decision of the Tax Court disallowing federal income tax deductions of a little more than $1,000 in each of two years, representing Moss's share of his law firm's lunch expense at the Cafe Angelo in Chicago. 80 T.C. 1073. The Tax Court's decision in this case has attracted some attention in tax circles because of its implications for the general problem of the deductibility of business meals. See, e.g., McNally, Vulnerability of Entertainment and Meal Deductions 212 Under the Sutter Rule, 62 Taxes 184 (1984). Moss was a partner in a small trial firm specializing in defense work, mostly for one insurance company. Each of the firm's lawyers carried a tremendous litigation caseload, averaging more than 300 cases, and spent most of every working day in courts in Chicago and its suburbs. The members of the firm met for lunch daily at the Cafe Angelo near their office. At lunch the lawyers would discuss their cases with the head of the firm, whose approval was required for most settlements, and they would decide which lawyer would meet which court call that afternoon or the next morning. Lunchtime was chosen for the daily meeting because the courts were in recess then. The alternatives were to meet at 7:00 a.m. or 6:00 p.m., and these were less convenient times. There is no suggestion that the lawyers dawdled over lunch, or that the Cafe Angelo is luxurious. The framework of statutes and regulations for deciding this case is simple, but not clear. Section 262 of the Internal Revenue Code (Title 26) disallows, "except as otherwise expressly provided in this chapter," the deduction of "personal, family, or living expenses." Section 119 excludes from income the value of meals provided by an employer to his employees for his convenience, but only if they are provided on the employer's premises; and section 162(a) allows the deduction of "all the ordinary and necessary expenses paid or incurred during the taxable year in carrying on any trade or business, including -- . . . (2) traveling expenses (including amounts expended for meals . . .) while away from home. . . ." Since Moss was not an employee but a partner in a partnership not taxed as an entity, since the meals were not served on the employer's premises, and since he was not away from home (that is, on an overnight trip away from his place of work, see United States v. Correll, 389 U.S. 299, (1967)), neither section 119 nor section 162(a)(2) applies to this case. The Internal Revenue Service concedes, however, that meals are deductible under section 162(a) when they are ordinary and necessary business expenses (provided the expense is substantiated with adequate records, see section 274(d)) even if they are not within the express permission of any other provision and even though the expense of commuting to and from work, a traveling expense but not one incurred away from home, is not deductible. Treasury Regulations on Income Tax § 1.262-1(b)(5); Fausner v. Commissioner, 413 U.S. 838, (1973) (per curiam). The problem is that many expenses are simultaneously business expenses in the sense that they conduce to the production of business income and personal expenses in the sense that they raise personal welfare. This is plain enough with regard to lunch; most people would eat lunch even if they didn't work. Commuting may seem a pure business expense, but is not; it reflects the choice of where to live, as well as where to work. Read literally, section 262 would make irrelevant whether a business expense is also a personal expense; so long as it is ordinary and necessary in the taxpayer's business, thus bringing section 162(a) into play, an expense is (the statute seems to say) deductible from his income tax. But the statute has not been read literally. There is a natural reluctance, most clearly manifested in the regulation disallowing deduction of the expense of commuting, to lighten the tax burden of people who have the good fortune to interweave work with consumption. To allow a deduction for commuting would confer a windfall on people who live in the suburbs and commute to work in the cities; to allow a deduction for all business-related meals would confer a windfall on people who can arrange their work schedules so they do some of their work at lunch. Although an argument can thus be made for disallowing any deduction for business meals, on the theory that people have to eat whether they work or not, the result would be excessive taxation of people who spend more money on business meals because they are business meals 213 than they would spend on their meals if they were not working. Suppose a theatrical agent takes his clients out to lunch at the expensive restaurants that the clients demand. Of course he can deduct the expense of their meals, from which he derives no pleasure or sustenance, but can he also deduct the expense of his own? He can, because he cannot eat more cheaply; he cannot munch surreptitiously on a peanut butter and jelly sandwich brought from home while his client is wolfing down tournedos Rossini followed by souffle au grand marnier. No doubt our theatrical agent, unless concerned for his longevity, derives personal utility from his fancy meal, but probably less than the price of the meal. He would not pay for it if it were not for the business benefit; he would get more value from using the same money to buy something else; hence the meal confers on him less utility than the cash equivalent would. The law could require him to pay tax on the fair value of the meal to him; this would be (were it not for costs of administration) the economically correct solution. But the government does not attempt this difficult measurement; it once did, but gave up the attempt as not worth the cost, see United States v. Correll, supra, 389 U.S. at 301 n.6. The taxpayer is permitted to deduct the whole price, provided the expense is "different from or in excess of that which would have been made for the taxpayer 's personal purposes." Sutter v. Commissioner, 21 T.C. 170, 173 (1953). Because the law allows this generous deduction, which tempts people to have more (and costlier) business meals than are necessary, the Internal Revenue Service has every right to insist that the meal be shown to be a real business necessity. This condition is most easily satisfied when a client or customer or supplier or other outsider to the business is a guest. Even if Sydney Smith was wrong that "soup and fish explain half the emotions of life," it is undeniable that eating together fosters camaraderie and makes business dealings friendlier and easier. It thus reduces the costs of transacting business, for these costs include the frictions and the failures of communication that are produced by suspicion and mutual misunderstanding, by differences in tastes and manners, and by lack of rapport. A meeting with a client or customer in an office is therefore not a perfect substitute for a lunch with him in a restaurant. But it is different when all the participants in the meal are coworkers, as essentially was the case here (clients occasionally were invited to the firm's daily luncheon, but Moss has made no attempt to identify the occasions). They know each other well already; they don't need the social lubrication that a meal with an outsider provides -- at least don't need it daily. If a large firm had a monthly lunch to allow partners to get to know associates, the expense of the meal might well be necessary, and would be allowed by the Internal Revenue Service. See Wells v. Commissioner, T.C. Memo 1977-419, 1977 T.C. Memo 419, 36 T.C.M. (CCH) 1698, 1699 (1977), aff'd without opinion, 626 F.2d 868 (9th Cir. 1980). But Moss's firm never had more than eight lawyers (partners and associates), and did not need a daily lunch to cement relationships among them. It is all a matter of degree and circumstance (the expense of a testimonial dinner, for example, would be deductible on a morale-building rationale); and particularly of frequency. Daily -- for a full year -- is too often, perhaps even for entertainment of clients, as implied by Hankenson v. Commissioner, T.C. Memo 1984-200, 1984 T.C. Memo 200, 47 T.C.M. 1567, 1569 (1984), where the Tax Court held nondeductible the cost of lunches consumed three or four days a week, 52 weeks a year, by a doctor who entertained other doctors who he hoped would refer patients to him, and other medical personnel. We may assume it was necessary for Moss's firm to meet daily to coordinate the work of the firm, and also, as the Tax Court found, that lunch was the most convenient time. But it does not follow that the expense of the lunch was a necessary business expense. The members of the firm had to eat somewhere, and the Cafe Angelo was both convenient and not too expensive. They do not claim to have 214 incurred a greater daily lunch expense than they would have incurred if there had been no lunch meetings. Although it saved time to combine lunch with work, the meal itself was not an organic part of the meeting, as in the examples we gave earlier where the business objective, to be fully achieved, required sharing a meal. The case might be different if the location of the courts required the firm's members to eat each day either in a disagreeable restaurant, so that they derived less value from the meal than it cost them to buy it, cf. Sibla v. Commissioner, 611 F.2d 1260, 1262 (9th Cir. 1980); or in a restaurant too expensive for their personal tastes, so that, again, they would have gotten less value than the cash equivalent. But so far as appears, they picked the restaurant they liked most. Although it must be pretty monotonous to eat lunch the same place every working day of the year, not all the lawyers attended all the lunch meetings and there was nothing to stop the firm from meeting occasionally at another restaurant proximate to their office in downtown Chicago; there are hundreds. An argument can be made that the price of lunch at the Cafe Angelo included rental of the space that the lawyers used for what was a meeting as well as a meal. There was evidence that the firm's conference room was otherwise occupied throughout the working day, so as a matter of logic Moss might be able to claim a part of the price of lunch as an ordinary and necessary expense for work space. But this is cutting things awfully fine; in any event Moss made no effort to apportion his lunch expense in this way. AFFIRMEDMore on Taxes Meal Deductions
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POSTU-129381-09 5
What is ultimately at issue in this matter is the extent to which Taxpayer can deduct the
costs it incurs to provide its employees with food and beverages.
Although the Taxpayer is entitled to deduct these costs as trade or business expenses
under section 162, section 274(n) limits the extent of this deduction. Namely, section
274(n)(1) limits the Taxpayer’s deduction to 50 percent of these costs.
The expenses are excepted from this 50 percent limitation if they are excludable as de
minimis fringe benefits under section 132(e). The conclusion that these meals are
excludable under section 119 is not dispositive of the issue of whether they are
excludable under section 132(e).
The legislative history of section 274(n) clarifies that the 50 percent limitation applies
even to expenses associated with meals that are excludable under section 119. H.R.
Conf. Rep. 99-841 specifies that the 50 percent limitation applies to “the amount of any
deduction otherwise allowable for meal expenses, including . . . meals furnished on an
employer’s premises to its employees (whether or not such meals are excludable from
the employee’s gross incomes under sec. 119).” This conference report further
indicates that Congress did not intend for this limitation to apply to meals excludable
only under section 119 when it stated that the exception to the limitation applied only to:
(1 ) reimbursed meal expenses (in which case the employer or person
making the reimbursement is subject to the 80-percent rule); (2) employerfurnished
meals that are excludable from the employee's gross income as
de minimis fringes under Code section 132(e) (including meals at certain
eating facilities excludable under sec. 132(e)(2)); (3) meals fully taxed to
the recipient as compensation; and (4) items sold to the public (such as
expenses incurred by restaurants or dinner theaters for food or
entertainment provided to their customers), or furnished to the public as
samples or for promotion (such as expenses incurred by a hotel in
furnishing complimentary lodging to potential customers).
In sum, this conference committee report specifies both that the 50 percent limitation
applies to provision of meals that are excludable only under section 119, and that the
provision of meals must satisfy the particular requirements of section 132(e)(2) to be
exempted from this 50 percent limitation.
Taxpayer asserts that the costs are, indeed, excludable under section 132(e)(2). The
Ninth Circuit’s decision in Boyd Gaming Corp. v. Comm’r, 177 F.3d 1096 (9th Cir.
1999), lends some support to this argument. The court held in Boyd that an employerprovided
meal meets the revenue/direct operating cost test of section 132(e)(2) if the
employee could exclude the value of that meal under section 119. As noted above, it
appears that employees could exclude the value of the majority—if not all—of the meals
at issue in the present matter under section 119. These meals therefore meet the
POSTU-129381-09 5
What is ultimately at issue in this matter is the extent to which Taxpayer can deduct the
costs it incurs to provide its employees with food and beverages.
Although the Taxpayer is entitled to deduct these costs as trade or business expenses
under section 162, section 274(n) limits the extent of this deduction. Namely, section
274(n)(1) limits the Taxpayer’s deduction to 50 percent of these costs.
The expenses are excepted from this 50 percent limitation if they are excludable as de
minimis fringe benefits under section 132(e). The conclusion that these meals are
excludable under section 119 is not dispositive of the issue of whether they are
excludable under section 132(e).
The legislative history of section 274(n) clarifies that the 50 percent limitation applies
even to expenses associated with meals that are excludable under section 119. H.R.
Conf. Rep. 99-841 specifies that the 50 percent limitation applies to “the amount of any
deduction otherwise allowable for meal expenses, including . . . meals furnished on an
employer’s premises to its employees (whether or not such meals are excludable from
the employee’s gross incomes under sec. 119).” This conference report further
indicates that Congress did not intend for this limitation to apply to meals excludable
only under section 119 when it stated that the exception to the limitation applied only to:
(1 ) reimbursed meal expenses (in which case the employer or person
making the reimbursement is subject to the 80-percent rule); (2) employerfurnished
meals that are excludable from the employee's gross income as
de minimis fringes under Code section 132(e) (including meals at certain
eating facilities excludable under sec. 132(e)(2)); (3) meals fully taxed to
the recipient as compensation; and (4) items sold to the public (such as
expenses incurred by restaurants or dinner theaters for food or
entertainment provided to their customers), or furnished to the public as
samples or for promotion (such as expenses incurred by a hotel in
furnishing complimentary lodging to potential customers).
In sum, this conference committee report specifies both that the 50 percent limitation
applies to provision of meals that are excludable only under section 119, and that the
provision of meals must satisfy the particular requirements of section 132(e)(2) to be
exempted from this 50 percent limitation.
Taxpayer asserts that the costs are, indeed, excludable under section 132(e)(2). The
Ninth Circuit’s decision in Boyd Gaming Corp. v. Comm’r, 177 F.3d 1096 (9th Cir.
1999), lends some support to this argument. The court held in Boyd that an employerprovided
meal meets the revenue/direct operating cost test of section 132(e)(2) if the
employee could exclude the value of that meal under section 119. As noted above, it
appears that employees could exclude the value of the majority—if not all—of the meals
at issue in the present matter under section 119. These meals therefore meet the
Holiday Party Tax-deductible?? Taxes
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NEW YORK (MarketWatch) — If all the talk about tax policies has you worried, you might look to your own holiday party for a little tax break.Let’s face it: parties can be downright expensive, especially if you add a little entertainment.But whether you’re a homemaker, a business owner trying to expand your reach, or someone who just wants to spread a little good cheer, there are ways to make an event tax-deductible. Read how more Americans are in a giving mood again.Here are three ideas:1.Building the businessIf you have a party that’s primarily for clients or potential clients, the expenses are clearly deductible because its purpose is for business. That means everything from the food, the booze and even the entertainment are deductible, as long as it was a “reasonable” expense.“If you had 30 people and spent $20,000, that might be unreasonable,” said Vince Batyr, a certified public accountant in Tarrytown, N.Y. “In that case, you need to be ready to explain: ‘Hey, I had hedge-fund managers who are used to $800 bottles of wine.’ And that actually might be reasonable, whereas in another situation it might not.”
Thinking about including some personal friends or family members to this “business” event? Batyr cautions against inviting too many. After all, the event’s primary purpose should be business. It’s safer to have significantly more than 50% who are business related. He also encourages clients to keep a list of who attended and the relationship in case you’re ever audited and your memory goes sour.Remember that business expenses that fall under “meals and entertainment” are only 50% deductible, whereas a marketing event for business purposes would be entirely deductible.“A town will have an open house for a retail store — that's clearly marketing and not 'meals and entertainment,’” Batyr said, “so there you can enjoy a 100% deduction.”Still, at a minimum, a $5,000 business-related party for someone in the 40% tax bracket (federal and state) results in an out-of-pocket cost of $4,000 for the party, at the 50% deduction rate (half of $5,000 is $2,500, and 40% of that adds up to $1,000 off your tax bill). Read about tax strategies for charitable giving.2. Do some goodWhat about those parties where guests are asked to bring a gift for a local charity? Read how one teenager’s nonprofit raised thousands of dollars for research.“At the end of the day, everything must pass a common test: is it reasonable?” Batyr said. “Are you disguising your party for deductible purposes or is this really legitimate?”He suggests making the charitable nature of the event a part of the party plan and clearly indicating to guests the purpose of the event. Coordinating with the charity organization in advance — and including their logo on your invitation — is also a way of avoiding any question about the event’s purpose.
Three ways to make a holiday party tax-deductible - MarketWatch
NEW YORK (MarketWatch) — If all the talk about tax policies has you worried, you might look to your own holiday party for a little tax break.Let’s face it: parties can be downright expensive, especially if you add a little entertainment.But whether you’re a homemaker, a business owner trying to expand your reach, or someone who just wants to spread a little good cheer, there are ways to make an event tax-deductible. Read how more Americans are in a giving mood again.Here are three ideas:1.Building the businessIf you have a party that’s primarily for clients or potential clients, the expenses are clearly deductible because its purpose is for business. That means everything from the food, the booze and even the entertainment are deductible, as long as it was a “reasonable” expense.“If you had 30 people and spent $20,000, that might be unreasonable,” said Vince Batyr, a certified public accountant in Tarrytown, N.Y. “In that case, you need to be ready to explain: ‘Hey, I had hedge-fund managers who are used to $800 bottles of wine.’ And that actually might be reasonable, whereas in another situation it might not.”
Thinking about including some personal friends or family members to this “business” event? Batyr cautions against inviting too many. After all, the event’s primary purpose should be business. It’s safer to have significantly more than 50% who are business related. He also encourages clients to keep a list of who attended and the relationship in case you’re ever audited and your memory goes sour.Remember that business expenses that fall under “meals and entertainment” are only 50% deductible, whereas a marketing event for business purposes would be entirely deductible.“A town will have an open house for a retail store — that's clearly marketing and not 'meals and entertainment,’” Batyr said, “so there you can enjoy a 100% deduction.”Still, at a minimum, a $5,000 business-related party for someone in the 40% tax bracket (federal and state) results in an out-of-pocket cost of $4,000 for the party, at the 50% deduction rate (half of $5,000 is $2,500, and 40% of that adds up to $1,000 off your tax bill). Read about tax strategies for charitable giving.2. Do some goodWhat about those parties where guests are asked to bring a gift for a local charity? Read how one teenager’s nonprofit raised thousands of dollars for research.“At the end of the day, everything must pass a common test: is it reasonable?” Batyr said. “Are you disguising your party for deductible purposes or is this really legitimate?”He suggests making the charitable nature of the event a part of the party plan and clearly indicating to guests the purpose of the event. Coordinating with the charity organization in advance — and including their logo on your invitation — is also a way of avoiding any question about the event’s purpose.
Are clothing, and food tax deductible? taxes
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....................
Only clothing that is required for your job, or food eaten as part of your business (i.e. entertaining clients, out of town trips, etc.).
It depends what your job is. As an actor I can deduct certain purchases, movie rentals, etc. Talk to a tax professional.
Oh, don't forget the mileage deduction for business travel
..................
50% of LEGITIMATE meals are deductible (say out of town trip, spent overnight in a hotel). So is customer entertainment, but each receipt must show the business purpose and the client who was present. Claiming lunch because it was during business hours doesn't count.
As for clothes, steel tipped safety shows can be deductible, stage costumes and specialized wear are deductible. Suits are not; jeans are not; anything you'd be willing to wear in public, no.
As for saving valid receipts--7 LONG years.
..................
There’s a lot of confusion among taxpayers about what meal and entertainment expenses they can legitimately deduct as business expenses on their tax returns. Professional tax preparers aren’t in complete agreement on the subject either. Not too surprising, considering the length and complexity of the Internal Revenue Code.As I said in an earlier article, in order to deduct any expense as a business deduction, it has to beordinary, necessary, and reasonable based on the facts and circumstances. Because the deductibility of business expenses is one of the 10 most litigated tax issues, you should discuss your individual situation with your CPA or tax pro.That said, I’ll explain the regulations as I understand them for
Are clothing, and food tax deductible?
I know that gas, office supplies and office equipment are tax deductible for your job. If you know of anything else please let me know. And how long do you need to save all of your recepits in case you are audited.....................
Only clothing that is required for your job, or food eaten as part of your business (i.e. entertaining clients, out of town trips, etc.).
It depends what your job is. As an actor I can deduct certain purchases, movie rentals, etc. Talk to a tax professional.
Oh, don't forget the mileage deduction for business travel
..................
50% of LEGITIMATE meals are deductible (say out of town trip, spent overnight in a hotel). So is customer entertainment, but each receipt must show the business purpose and the client who was present. Claiming lunch because it was during business hours doesn't count.
As for clothes, steel tipped safety shows can be deductible, stage costumes and specialized wear are deductible. Suits are not; jeans are not; anything you'd be willing to wear in public, no.
As for saving valid receipts--7 LONG years.
..................
When is That Meal Tax Deductible?
There’s a lot of confusion among taxpayers about what meal and entertainment expenses they can legitimately deduct as business expenses on their tax returns. Professional tax preparers aren’t in complete agreement on the subject either. Not too surprising, considering the length and complexity of the Internal Revenue Code.As I said in an earlier article, in order to deduct any expense as a business deduction, it has to beordinary, necessary, and reasonable based on the facts and circumstances. Because the deductibility of business expenses is one of the 10 most litigated tax issues, you should discuss your individual situation with your CPA or tax pro.That said, I’ll explain the regulations as I understand them for- unreimbursed expenses that are incurred
- in your local area
- client
- customer or
- employee
- directly related or
- associated
- nightclubs
- theaters
- sporting events and
- cocktail parties
- cocktail lounges
- country clubs
- golf clubs
- athletic clubs or
- vacation resorts
- amount
- date
- place
- purpose of the expense
- nature of the discussion and
- relationship of the people attending
Thursday, July 5, 2012
Pathophysiology of Paget's disease (Osteitis deformans)
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BASIC PHYSIOLOGY OF NORMAL BONE RESORPTION AND FORMATION :
*Osteoclast maturation is regulated by various factors, such as Receptor Activator of Nuclear Factor-kappaB (NF-kappaB) Ligand (RANKL). RANKL can exist as a soluble form and binds to the osteoclast receptor RANK.
*This binding activates osteoclast differentiation via the translocation of NF-kappaB into the nucleus by intermediates such as Tumor Necrosis Factor (TNF) Receptor-Associated Factor 6 (TRAF6).
*RANKL signals can be blocked by a soluble RANKL-binding decoy receptor, osteoprotegerin (OPG), produced by osteoblasts.
*Vacuolar H+-ATPase pump (H+), matrix metalloproteinase (MMP), Cathepsin K and Tartrate-Resistant Acid Phosphatase (TRAcP) are involved in osteoclast activity.
*This picture above helps us in understanding the pathophysiology behind PAGET'S disease :
*PATHOPHYSIOLOGY OF PAGET'S DISEASE:
- The principal abnormality in Paget disease is the increased number and activity of osteoclasts. - Pagetic osteoclasts are large, increased 10- to 100-fold in number, and have a greater number of nuclei (as many as 100 compared to 3–5 nuclei in the normal osteoclast). - The overactive osteoclasts may create a sevenfold increase in resorptive surfaces and an erosion rate of 9 microg/d (normal is 1 microg/d).
- Several causes for the increased number and activity of pagetic osteoclasts have been identified: (1) Osteoclastic precursors are hypersensitive to 1,25(OH)2D3; (2) Osteoclasts are hyperresponsive to RANK ligand (RANKL), the osteoclast stimulatory factor that mediates the effects of most osteotropic factors on osteoclast formation; (3) Marrow stromal cells from pagetic lesions have increased RANKL expression; (4) Osteoclast precursor recruitment is increased by interleukin (IL) 6, which is increased in the blood of patients with active Paget disease and is overexpressed in pagetic osteoclasts; (5) Expression of the proto-oncogene c-fos, which increases osteoclastic activity, is increased; and (6) The antiapoptotic oncogene Bcl-2 in pagetic bone is overexpressed. Numerous osteoblasts are recruited to active resorption sites and produce large amounts of new bone matrix. As a result, bone turnover is high and bone mass is normal or increased, not reduced.
- The characteristic feature of Paget disease is increased bone resorption accompanied by accelerated bone formation. - An initial osteolytic phase involves prominent bone resorption and marked hypervascularization. - Radiographically, this manifests as an advancing lytic wedge, or "blade of grass" lesion. - The second phase is a period of very active bone formation and resorption that replaces normal lamellar bone with haphazard (woven) bone. - The mosaic pattern of woven bone is structurally inferior and can bow and fracture more readily. - At the same time, fibrous connective tissue may replace normal bone marrow. - In the final sclerotic phase, bone resorption declines progressively and leads to a hard, dense, less vascular pagetic or mosaic bone, which represents the so-called burned-out phase of Paget disease. - All three phases may be present at the same time at different skeletal sites.
*Acutely marginated bone demineralization during lytic phase in skull - OSTEOPOROSIS CIRCUMSCRIPTA.
*Acutely marginated demineralization of long bones - BLADE OF GRASS SIGN and FLAME SHAPED MARGIN.
*Mixed lytic and sclerotic phase in spine - PICTURE FRAME VERTEBRAE
*Mixed lytic and sclerotic phase in skull - COTTON WOOL SKULL.
*Osteoclast maturation is regulated by various factors, such as Receptor Activator of Nuclear Factor-kappaB (NF-kappaB) Ligand (RANKL). RANKL can exist as a soluble form and binds to the osteoclast receptor RANK.
*This binding activates osteoclast differentiation via the translocation of NF-kappaB into the nucleus by intermediates such as Tumor Necrosis Factor (TNF) Receptor-Associated Factor 6 (TRAF6).
*RANKL signals can be blocked by a soluble RANKL-binding decoy receptor, osteoprotegerin (OPG), produced by osteoblasts.
*Vacuolar H+-ATPase pump (H+), matrix metalloproteinase (MMP), Cathepsin K and Tartrate-Resistant Acid Phosphatase (TRAcP) are involved in osteoclast activity.
*This picture above helps us in understanding the pathophysiology behind PAGET'S disease :
*PATHOPHYSIOLOGY OF PAGET'S DISEASE:
- The principal abnormality in Paget disease is the increased number and activity of osteoclasts. - Pagetic osteoclasts are large, increased 10- to 100-fold in number, and have a greater number of nuclei (as many as 100 compared to 3–5 nuclei in the normal osteoclast). - The overactive osteoclasts may create a sevenfold increase in resorptive surfaces and an erosion rate of 9 microg/d (normal is 1 microg/d).
- Several causes for the increased number and activity of pagetic osteoclasts have been identified: (1) Osteoclastic precursors are hypersensitive to 1,25(OH)2D3; (2) Osteoclasts are hyperresponsive to RANK ligand (RANKL), the osteoclast stimulatory factor that mediates the effects of most osteotropic factors on osteoclast formation; (3) Marrow stromal cells from pagetic lesions have increased RANKL expression; (4) Osteoclast precursor recruitment is increased by interleukin (IL) 6, which is increased in the blood of patients with active Paget disease and is overexpressed in pagetic osteoclasts; (5) Expression of the proto-oncogene c-fos, which increases osteoclastic activity, is increased; and (6) The antiapoptotic oncogene Bcl-2 in pagetic bone is overexpressed. Numerous osteoblasts are recruited to active resorption sites and produce large amounts of new bone matrix. As a result, bone turnover is high and bone mass is normal or increased, not reduced.
- The characteristic feature of Paget disease is increased bone resorption accompanied by accelerated bone formation. - An initial osteolytic phase involves prominent bone resorption and marked hypervascularization. - Radiographically, this manifests as an advancing lytic wedge, or "blade of grass" lesion. - The second phase is a period of very active bone formation and resorption that replaces normal lamellar bone with haphazard (woven) bone. - The mosaic pattern of woven bone is structurally inferior and can bow and fracture more readily. - At the same time, fibrous connective tissue may replace normal bone marrow. - In the final sclerotic phase, bone resorption declines progressively and leads to a hard, dense, less vascular pagetic or mosaic bone, which represents the so-called burned-out phase of Paget disease. - All three phases may be present at the same time at different skeletal sites.
*Acutely marginated bone demineralization during lytic phase in skull - OSTEOPOROSIS CIRCUMSCRIPTA.
*Acutely marginated demineralization of long bones - BLADE OF GRASS SIGN and FLAME SHAPED MARGIN.
*Mixed lytic and sclerotic phase in spine - PICTURE FRAME VERTEBRAE
*Mixed lytic and sclerotic phase in skull - COTTON WOOL SKULL.
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