Homeostasis se & Calcium - metabolic Bone Disea Week Three: Metal Mrs. Bony's Back Pain INTRODUCTION id i disease and calcium This week objectives are to discuss and understand metabolic bone af ‘objectives ar pe of this week consists of the oF \Omeostasis, both is common for elderly group patients. The sc sm homeostasis, physiology and P: lifestyle, and hormonal influe 1BY and biochemistry of calci sathophysiology of metabolic Physioloy at se = a snces to the disease, the bone disease in general, the role of nutrition, role of medical and surgical management of the disease. the case, but will be discussed in lectures. Some of these objectives are not covered WEEK OBJECTIVES Understand bone-remodeling process. Describe bone density changes across the life cycles if 2. 3. Line out metabolic bone disease (osteomalacia, Ricket’s, Paget, Osteoporosis) 4. Explain pathogenesis of osteoporosis. 5. Line out risk factors of osteoporosis. 6. Describe investigative findings in osteoporosis (laboratory, x-ray, bone den: 7. Describe the physiological balance of calcium and phosphate, the roles of calcitonin, vitamin D hormones, the Gl tract and kidney in this balance, 8. Line out the management of osteoporosis. OVERVIEW Osteoporosis, or porous bone, is a disease chai deterioration of bone tissue, leading to Osteoporosis is a major underlying ¢ persons in general. A fall, blow, oF| can easily cause one or more Osteoporosis is symptoms. People may a sudden strain,lly be felt or seen in HS (severely st higher in women than ‘a Certatn risk fa individuat's ‘may initial as kyphosi the form of severe back pain, loss of height, or spinal deformities such SPE Bosture). The risk of developing osteoporosis increases with age andi men, ket ‘Ors are linked to the development of osteoporosis and contribute to an 100d Of developing the disease. Many people with osteoporosis have several risk “Getler The chances of developing osteoporosis are greater for a woman. Women have less.bone tissue and lose bone faster than men because of the changes that happen with menopause. * ABE~ The older someone is, the greater risk of osteoporosis. The bones become thinner and weaker as they age. * Body size Small, thin-boned women are at greater risk. Ethnicity ~ Caucasian and Asian women are at highest risk. African American and Hi women have a lower but significant risk. Family history ~ Fracture risk may be due, in part, to heredity. People whose pa history of fractures also seem to have reduced bone mass and may be at risk for| Risk factors that can be changed: © Sex hormones’ Abnormal absence of menstrual periods (amenorrh (menopause), and low testosterone level in men can bring on osteopt * Anorexia nervosa ~ Characterized by an irrational fear of wel increases the risk for osteoporosis. * Calcium and vitamin D intake ~ A lifetime diet low in c more prone to bone loss. ‘+ Medication use~ Long-term use of glu of bone density and fractures. + Ufestyle— An inactive lifestyle o © Cigarette smoking ~ Cigaret Medical Treatment\d medications: Treatment combines? exer safetY Me y diet is important to Ree. and vitamin Oxin 2 health in the treatment of Getting adequate amounts of calcium, phosphorus ements are used i encourage bone growth and maintain health. Witamin O suppl osteoporosis. Weight-bearing exercise, 20%tt6, 3-4 /miagau eas os ae ne loss, Modest Some recent studies suggest that weight-bearing exercise may reduce bearing exercise, such as walking, jogging: hiking, dancing, is recommendes Saas a Positive effects, the foremost being an increase in bone density. Exercise also incre for falls. Twenty minutes of exercise 3 or 4 xd. Those have several ses strength, -£e0rdination, and balance, thereby reducing the ris! times per week is recommended. Women should consult their physicians when beginning 2° exercise program. Safety Prevention. of fracture in susceptible patients is the primary goal of intervention. Strategies to Prevent falls are important in elderly patients who may fall frequently for a variety of reasons, such as from effects of drugs. Specific’environmental interventions can minimize home hazards increase the chances of falling. Measures taken to prevent falls are also part of the treatment * Avoid slippery surfaces * Install hand rails * Keep surfaces smooth and uncluttered * Provide adequate lighting * Useacane or walker + Wear rubber-soled, flat shoes + Wear eyeglasses The medications that are approved for the management of osteops resorption agents (estrogen, alendronate, risedronate, and there is now only one: teriparatide. These ag reduce fracture risk by approximately 50% been shown to reduce the risk of risedronate have reduced the risk of hi"und region, and the pain b. thing’in fac + lifting heavy thing In local around region, and the pain ¥ecome more intense after lifting heavy to reinforce the e. Surgical procedure 2%, Represent small areas of microfracture within the spine. Surgical r in patients with osteoporosis, now vertebrae with compression fractures, which are common in pati Suite common procedure. The procedures are called vat lasty’or by styrwhich ty’or kyphoplasty Procedures are called vartebroptasty’ : * tOlseting an acrylic compound e .ed vertebra to stabilize the weakened bone i into the collapsed vertebi ech ati adiology suite and treatment of éach affected ‘Re Procedure is performed in an operating room or radiology vertebra takes approximately 1 hour.TUTORIALS PAGEL idetifein rural area % seeing working 35 2 in on her: back since 1 rts : circ. She PO ich had someBUmPY and localized on the Ws. tony 8 soa 8 {you for the first time in the medical school vot ap te fees the 0 Foad:by ambulance: she describes her Ne apes some pain sean ame sila anaes ‘eels pain that comes and goon he upper shealo notes tha ston shore tan Dette cor inas Sedain. neuro, murcte. 2 Explain your reasons! fom oma> 1. Whats the most probable source ofthe pain? Explain Your siaior a IDimcheASGt tne pig doeare matey chocacerstic of peuralpaiy resiculer racic vertebra. ‘muscle pain so the mast probable source of pain in this case's from thoracic verte 2. What is the most likely mechanism of injury in this case? The most likely mechanism of injury is compression fracture, which is caused by force perpendicular to the spine. 3. What is the cause of her chronic upper back pain? There are several things to consider about her condition. It is consider as fracture. It brings us to a wide range of differential diagnosis such as: ‘* Pathologic fracture from neoplasm “ © Osteomalacia v + Paget's disease v * Infections (such as tuberculosis) ~ + Fibrous dysplasia © Osteopenia v © Osteoporosis ¥ inp ¥ Pathologic fracture from occur through an area invasion. The most co prostatic cancer, lung Ahatomi spine Cervicat* Not enough vitamin Din the diet + Noten. ae Tan exposure to sung which prods amin Dn the body labsorption of vitamin D by the intestines Other conditions thatmay cause osteomalacia include: * Hereditary or acquired disorders of vitamin D metabolism + Kidney failure and acidosis * Phosphate depletion associated with not enough phosphates in the diet + Cancer * Side effects of medications used to treat seizures + Uverdisease Use of very strong sunscreen, li sure of the body to sunlight, short days of sunli and_smog are factors that reduce formation of vitamin D in the body. Risk factors for ‘osteomalacia are related to the causes. In the elderly, there is an increased risk among people \doors and those who avoid milk because of lactose intolerance. who tend to remait Paget's disease of the bone (osteitis deformans) is a chronic skeletal disorder, which may result in enlarged. or deformed bones in one or more regions of the skeleton. Excessive b breakdown and formation can result in bone, which 's dense but fragile. in many cases may be no Paget's disease symptoms. Many patients who have Paget's disease do not have it since the bone disease may be so mild that itis not diagnosed. Sometimes, Paget's disease symptoms are confused with arthritis or other bone disorderss It the diagnosis is made only after complications have developed. When Paget's do occur, they are usually in advanced cases, and they can inch fractures, bowing of limbs, and hearing loss if Paget's disease The causes of Paget's disease are still not disease may be caused by a “slow virus” in years before symptoms appear. There sometimes present in more than oneceptible to the sus, ce Paget's disease are SUSCED Feason that members of a family who hav' frequently in th virus. Paget's disease Occurs most freq : Any bone can be affected in Paget's disease- thighs and lower Fees) SOME patients will awetclrennceemeretihnioverenrertes | three, or more affected bones. have only one affected bone, while others may have two, three, c spondiuils ture andy ial Jon of the bone,can ceange'ttrertiorre Str defections (such astuberculosis) the infection of the at wieone but (ote Cause thesbone-becomesteagite. The local process can take Pl commonly at the hip, spine and wrist. a bensoLan dpe jingsmesenchymé that brows dysplasia isa skeletal developmental anomaly of the bonésfosmisaeme: pe - ne it manifests as a defect in osteoblastic differentiation and maturation. Virtually any bor ‘ sia, the body can be affected. itis a nonhereditary disorder of unknown cause. In fibrous dysplasi medullary bone is replaced by fibrous tissue, which appears radiolucent on radiographs, with the classically described ground-glass appearance, Trabeculae of woven bone contain fluid-filled contributes to the cysts that are embedded largely in collagenous fibrous matrix, wi generalized hazy appearance of the bone. tow bone mass that is not low enough to be diagnosed as osteoporosis, this is sor referred to as osteopenia, Low bone mass could be caused by many factors such as: © Heredity * the development of less-than-optimal peak bone mass in the youth * @medical condition or medication to treat such a condition that negativeh + Abnormaily accelerated bone loss, While not everyone who has low bone mass will develop osteoporosis, ‘mass is at higher risk for the disease and the resulting fractures. Osteoporosis, or porous bone, is a diseé deterioration of bone tissue, leading to of the hip, spine, and wrist. Men as can be prevented and treated.ptt 4. Explain why she nee She feels e : shorter bec Be therels shortening ofthe vertebral body and joints, so in return — “ouse decreased total height, TuroriaLy A. PAGE 2 She never had 2 Major injury before, but she underwent an ovarectomy AS was 37-year-oltl. She is not consuming drugs and | yow © not having regu ion excel 1. Is there any relationship between the history and the present symptoms? The relationship between ovarectomy and the Present symptoms is that the symptoms are ‘most likely happen due to osteoporotic bone. Ovarectomy is a Procedure to remove an ovarium, the effect of this procedure is that there is permanent and significant decrease of estrogen level. Low level of estrogen will reduce the bone perfusion and then will cz increase in bone loss. What other facts do you think you need to acquire about the history? On the history we need to know further about the Past procedure. bilateral, and does she have hormone replacement therapy or not.pr + anotene senor aytonornic TuToRIAt 1 PAGE3 put there is an found localized” rank and lower in defecation ;pnormalitys TOn physical examination there 16 90 $4 MN ctor ‘increase: kyphosts on thoracic region. On palpated © tenderness on mid-thoracic region. Skin es disturbance extremity is normal. Muscle power 5/5/5/5. There | ‘and micturition. ne yypothesis? Explain! 5 fi a 4. Are the findings in physical examination confirms you meaffai a neral pa The physical examination reveals that the pain is least Il Ee Soncths there are no sensoric or motoric disturbances. Kyphotic posture also SUE is most likely from bone origin. because pain 2. What are your differential diagnoses? © Osteoporosis /steovenia/ osteomotacis * Disc degeneration '* Muscle abnormality 3. What further examination do you need to confirm your working diagnosis? To establish the diagnosis we need lab results of complete blood sedimentation rate, serum calcium and phosphate level, serum parathy estrogen level. Beside lab findings we also need radiographic fi ) = Mdicntor oF OP 4 Ffacture tsk ~» DEXA - dual -energy xtay abso 4 o 4] norma bone denisey -1 aS Low bone Mase Cocteopenia ) ' -25 3 | presence of ofTUTORIAL 2 PAGEL ab results: M127 wan way W8C: 42.0004 Hesaom 53-45 ho Diff count: Pit: 250. 4 Serene ears Bhiermncn oo Sean pee ee Serimipherehars at eegran 5-4 EyPalmt 4-32 Serum estrogen: 10 pg/mmt 50-MOO Rac idiographic results are as, following (attachment) 1. Mention ‘he findings you found on the examination De the findings confirm your Work" diagnosis? * _tpboratory findings reveal that there are increased level of white blood count and erthrocyte sedimentation rate. There is also decrease level of serum estrogen. * Radiographic examination reveals compressed biconcave vertebral bodies with “ballooning” of the intervertebral disc, as well as rarefaction of all the bones: * All the lab findings and radiographic examination suggest that the most likely cause of this case is osteoporotic changes in vertebral bone. 2. Explain the pathomechanism of your working diagnosis? Describe the difference with other metabolic bone disease! Throughout the lifetime, old bone is removed (resorption) and new bone is added to the skeleton (formation). During childhood and teenage years, new bone is added faster th ‘ld bone is removed. As a result, bones become larger, heavier, and denser. Bone form: ‘outpaces resorption until peak bone mass (maximum bone density and strength) is r around age 30. After that time, bone resorption slowly begins to exceed bone form: For women, bone loss is fastest in the first few years after m continues into the postmenopausal years. Osteoporosis ~ which mainly may also affect men ~ will develop when bone resorption occurs replacement occurs too slowly. Osteoporosis is more likely to optimal peak bone mass during the bone-buil Mineralization is responsible foror slow phase, which takes ndary, and the $20 oa ible for as muct ‘The rapid increase In BMD over ing of the remodeling space” crease in BMD over the phase, occurring over a period of months, years. The second phase, which may be responsi ‘mineralization, is incomplete in high bone turnover stateS tw RPETE2 meokthd of taphosphanate therapy ts due 20 "AUN ® associated with the first phase of mineralization, while the slower" ae following years ts due to increased secondary mineralization allowed PY t bone tumover. Even the size and distribution of hydroxyapatite ith animal studies suggesting that @ crystals may affect the mix of small and large ‘mechanical properties of bone, ‘crystals are stronger than only large crystals or only small crystals. Bone matrix is the noncakcified portion of bone, 90% of which is collagen. It provides elasticity an flexibilty to bone. Inherited and acquired collagen fibrils, crosslinking, or non-collagenous proteins may have serious conseq\ bone strength and fracture risk. Mild forms of metabolic bone disease with abnormal collagen, such as osteogenesis imperfecta and Ehlers-Danlos syndrome, may sometimes: masquerade as postmenopausal osteoporosis. (decreased deposition and increased resorption) composed of type 1 disorders of the jwences on 3. Which cells are involved in the pathological process of this case? What are the factors can alter the activity of those cells? The bone cells include the osteoclast, the osteoblast and the osteocyte. consist of multi nucleated cells with a ruffled border. They are highly energi Consist of numerous nuclei, Golgi and mitochondrial bodies and secrete proteing lysis, chemicals, to dissolve the bone surface and dig pits into the bone, formed from hematopoietic progenitors ~ bone marrow origins cells, osteoclasts, which then mature into the more mature in active o becoming active and functional. The carbonic acid pat! into the cleft between the cell and the bo proteinase, mixed matrix metalloprote reduction in ph and lytic enzymes th digging a pit into the bone surface.The osteoclasts come under multiple cytokine influences. The surface of the osteoclasts Mave 2 receptor called RANK — receptor activator of nuclear factor — kappa beta. This binds RANK Ugand which is a soluble receptor of the TNF superfamily. RANK Ligand binds to the RANK receptor on the surface of the pre-fusion osteoclast, stimulating the cell to become multinucleated and activated. RANK Ligand, is produced by the osteoblast. The osteoblast is influenced by multiple other cytokines and hormones to produce RANK Ligand. MCE DEUS TET OUR TE CSO ETC e Loy eet Osteociast These cytokines include primarily, IL-6, IL-1 and tu However the prostaglandins, vitamin D., glucoco recombinant protein, as well as 1L11, all increase these hormones and cytokines is to stimulatTRE Sats emaine smerny temoraate RETEST fs The cect grotecss ymecrcnegere Cutecgromgec Sets o eerecethatar ths ining of Se ACD yes ane Dermares PRuCn < eceiaet 2) Gem ao sealants FAN 2 eae PREM RANK actuation ant sree 2y Pecucing emmeiast accuny wit FRAME Legos rene: | eal ete ase Be) eed BANK gard plays 2 key destruction. it iqvcheed io caste is and senior tof through this RANK Ligand ™ jgand, wher stiereh which will theo Gitinhibitors, eat LOU te his is a cell made from mesenchymal cells which mature to pre-osteoblast Cells. and then the mature osteoblast itself. Bone morphogenetic protein and WNT, stimulate the early differentiation to the Preosteoblast. The Preosteoblast is influenced by insulin like growth factor ILGF-1,to mature to the osteoblast. Parathyroid hormone and growth hormone, will both stimulate ILGF-1, Hence growth hormone and parathyroid hormone will both result in growth of the bone skeleton. The role of the osteoblast is to fill the but that has been done by the osteoclast. The early un- mineralized protein containing bone matrix, is called osteoid. The ‘osteoblast therefore grows the bony skeleton and osteoid becomes mineralized and calcified complete the cycle. Osteoblasts that are left within the layers in the reconstituted bone, form into the Osteocytes. These Osteocytes communicate with each other via canalicull Jong interdigitating cellular extensions, that enable communication between cells, of Osteocytes form a pressure and structural monitoring system within the bom therefore can identify microscopic cracks in the bone architecture and can cal ‘and osteoblasts to repair any microscopic damage. In fact bor ues through life, continually restori cycle that con osteoblasts, activate the osteoclast via RANK, approximately 12 days Reversal then occurs, replaced by osteoblasts, which layer oste becomes mineralized. This formation phiieciy es packer ue ext Preis eden mucro-crack Pree ading + an Certain risk factors are linked-to the development of osteoporosis and contribute to : H individual's ikelihood of developing the disease. Many people with osteoporosis have several ‘isk factors, but others who develop the disease have no known risk factors. There are some that cannot be changed and others that can be changed. Osteocytes have been rather neglected until recently but again play a:major role in regulating bone remodeling. They are the main source:of sclerostin, and they're responsive to a large variety of systemic hormones’ and also of course to mechanical stimuli: and their extensive canalicular connections with each other, and also with lining cells on the bone surface, whick ‘make them ideally placed to respond to mechanical stimuli and to initiate the appropriate b remodeling response. Osteocytes also produce FGF23, which is a major regulator of renal phosphate homeo acts/as a co-receptor for Klotho - a very interesting gene that is a suppressor of process in many tissuesin the body, including bone. Finally, Brendon Noble and his colleagues have shown data suggesting osteocytes may generate signals that activate osteoclast resorption and enable microdamage repair; 1 of the changes with aging is that tf viability and so maybe it is by this mechanismithat.o and to bone fragility in later life 4. Explain about surface phenomenatoned by the minaret, Under ae mies 204 thats synthesied fist os osteoid and subseauertlY (AATTUAO % UDHON: tho cnr formation always tclows abortion, 203 1% O10F Ord, (he amountray eaten bone remodeling stat of bane ae — Fevorbed and formed in tne young adut skeleton 2° aining- bone: mass. In humans, Yoremodelingn vce ‘=> 5, How estrogen level plays a role in this case? ‘As women enter menopause, the normal estrogen production by the ovaries decreases. Lower estrogen, blood levels leads to accelerated bone loss and osteoporosis. This process ‘occurs right after the onset of menopause and lasts for about 10 years. The bone loss con vary from less than 1% per year to above 5% per year, with an average of 2% per year: Estrogen replacement therapy (ERT) has been shown-to prevent bone loss, increase bone mass, and prevent bone fractures. It is useful in both preventing osteoporosis in postmenopausal women and in treating women who already have developed osteoporosis. 6. Mention other hormonal problems that can cause similar condition! Disturbance in parathyroid hormone balance may also cause bone resorption imbalan TUTORIAL 2 PAGE2 ‘The doctor prescribed thoracolumbar brace and NSAID. calcium’ supplement 1500 mg daily, vitamin D ‘once @ week and estrogen replacement ther mobilization and exposure to morning suntmobitzation and morning 4. What is the role of calcium, vitamin Dy a a Sere yore’ . Adequate calcium intake and adequate body 5" sal _ er, for maintaining bone mass and strength. Howey’ ca antiresorptive medications both in the prevention ant reat ea 0 Calcium is an essential nutrient necessary for the ProPS et muscles, nerves, and other body functions, 25 well as maintaining oR rst Calclum intake 1s important. for everyone, regardless whethe osteoporosis, Each day, the body loses calcium in the urine, feces, in the diet Is not sufficient to cover these be replaced by calcium in the diet. If calcium jn the diet osteoporosis joning of the hearts bones. Adequate e already has ‘and sweat. These losses have to ’ jum in the diet losses, the body takes calcium from the bones. Over time, insufficient calcium in jum intake can leads to negative calcium balance and bone loss (osteoporosis). Adequate calcium intal help prevent osteoporosis and increase bone mass and strength. The levels of ealcium intake recommended by The Nationalinstitutes of Health Consensus Conference on Osteoporosis are: 1. 800-mg/day for children ages 1-10 2. 41000 mg/day for men, premenopausal women, and postmenopausal women taking estrogen 3. 1200 mg/day for teenagers and young adults ages 11-24 4, 1500 mg/day for post menopausal women not taking estrogen’ 5. 1200mg-1500 mg/day for pregnant and nursing mothers These recommended levels of calcium intake are meant for all pe with established osteoporosis. Surveys have shown that the aver receives less than 500 milligrams of calcium per d In addition to good nutrition with adequi stopping smoking, and curtailing alcoho} treating osteoporosis. tt issknown that young men and bones with higher bone density thanand WOMEN StF. ie bong {his aBe-related bone loss, Prudent exercise is important to avoid Injury to already weakened bones. In patients over 40 and in those with conditions such as heart disease, obey, diabetes metitus, nigh blood Pressure, types and levels of exercise should be prescribed and monitored by their doctors: Finally, extreme levels of exercise (such as marathon running) may not be healthy for the bones. Marathon running in young women that leads to weight loss and loss of menstrual periods can actually cause osteoporosis, @itamin-D, in the form of calcifero! (vitamin D3) is a fat-soluble vitamin. It is found in food, but also can be made in your body after exposure to ultraviolet rays from the sun. Vitamin D rent function. Some forms are relatively inactive in the exists in several forms, each with a body, and have limited ability to function as a vitamin: The liver end kidneys help convert vvitamin:D to its active:hormoneyform known as calcitriol; so, in actual fact, vitamin D technically is Sunlight derived pro-hormone calcitriol. Vitamin Din its active pro-hormone form of calcitriol is important in determining how our cells express themselves and is vital in the production of various hormones and neurotransmitters (messengers in the brain). For the purpose of m clarity and understanding we will refer to calcitriol as vitamin D. The major biological function of vitamin O is to maintain normal blood levels of cal phosphorus. VitaminsD-helps:us’absorb calcium, and thus helps to form and i bones and teeth. It regulates bone mineralization in unison with a number minerals; and hormones. In short, without vitamin D, bones start to misshapen. Vitamin D prevents rickets in children, os Vitamin D is produced by skin in cespons sunlight. Vitamin D is important for osteopor 1. Vitamin D stimulatesthe absorptionweakens the that further depleted bone (osteomalacia) Lack of vitamin © causes calcium-dep! ‘bones and increases the risk for broken bones: si oe 3. Vitamin 0 along with adequate calcium (1200 mg of ses fractures in postmenoPa. ae some studies to increase bone mass and decrea! ses appeers sil 4. Furthermore, osteoarthritis (degenerative arthritis) of the pono Va BEE ee Patients who are deficient in vitamin D. Patients with osteo a viste one vitamin D are relatively low may benefit from increased witarm exposure. ip with the case 2. Explain when a person reach “Peak bone-mass”, and the relationshi} & 1p to age 30, there ‘The bone cycle varies during different times of life. In the growing years UF high turnover of formation and resorption. uring this phase, formation is greater than resorption and the bone grows. In the second phase of life during stability between the ages of 30 and 50, bone turnover remains prominent but formation equals resorption, and the bone is stabilized. In the early menopause however, this system becomes unstable because of a rise of resorption compared to formation with a high turnover state. The consequence is bone Joss during the early menopausal years: This will set the pace for the future. In the fourth days, in the elderly years, Bone turnover is low and resorption still exceeds formation, although at a much lower pace compared to menopause. Because we know that bone loss accelerates at menopause, we can assess peak bone mass before onset of menopause and assess risk for that individual, A bone mineral density lower than -2.5 standard deviation from the peak bone mass, is defined as osteoporosis: However any bone mass abovevor below -2.5 standard deviation, in the presence’of fracture! or previ fracture, defines the patient as having severe osteoporosis. 3. How is the mechanism of action of biphosponate and estrogen in this case? Bisphosphonate inhibit bone resorption by an effect on the osteoclasts. Bisphosphonates bind phosphonate groups in the hydroxyapatitie. of containing Bisphosphonates inhibit Farnesyl pyrophosphate synt prenylation of G-proteins. G-proteins are involved in the ruffled border of osteoclasts. On Bi becomes untuffled, and the jife span of the The Bisphosphonates drugs are badly about 5%, but from the'circulation, t}— content, and require specific instruction in their use. Generic products may have problems with absorption. Absorpti intestinal disease, Skeletal half life car ion is further aggravated in the presence of malabsorption or Once absorbed and bound to bone, they are remarkably consistent. in last as long as 10 years with the alendronate. EPILOGUE After set of therapies she was pain-free and back to work without much problems. She continuously receive HRT and having more healthy lifestyle to prevent the osteoporosis getting worse