densitometric criteria alone. biomarkers chemical biomarkers are a useful tool in detecting bone degradation. the enzyme cathepsin k breaks down type-i collagen, an important constituent in bones. prepared antibodies can recognize the resulting fragment, called a neoepitope, as a way to diagnose osteoporosis. increased urinary excretion of c-telopeptides, a type-i collagen breakdown product, also serves as a biomarker for osteoporosis. comparison of bone pathology condition calcium phosphate alkaline phosphatase parathyroid hormone comments osteopenia unaffected unaffected normal unaffected decreased bone mass osteopetrosis unaffected unaffected elevated unaffected thick dense bones also known as marble bone osteomalacia and rickets decreased decreased elevated elevated soft bones osteitis fibrosa cystica elevated decreased elevated elevated brown tumors paget's disease of bone unaffected unaffected variable (depending on stage of disease) unaffected abnormal bone architecture other measuring tools quantitative computed tomography (qct) differs from dxa in that it gives separate estimates of bmd for trabecular and cortical bone and reports precise volumetric mineral density in mg/cm3 rather than bmd's relative z-score. among qct's advantages: it can be performed at axial and peripheral sites, can be calculated from existing ct scans without a separate radiation dose, is sensitive to change over time, can analyze a region of any size or shape, excludes irrelevant tissue such as fat, muscle, and air, and does not require knowledge of the patient's subpopulation in order to create a clinical score (e.g. the z-score of all females of a certain age). among qct's disadvantages: it requires a high radiation dose compared to dxa, ct scanners are large and expensive, and because its practice has been less standardized than bmd, its results are more operator-dependent. peripheral qct has been introduced to improve upon the limitations of dxa and qct. quantitative ultrasound has many advantages in assessing osteoporosis. the modality is small, no ionizing radiation is involved, measurements can be made quickly and easily, and the cost of the device is low compared with dxa and qct devices. the calcaneus is the most common skeletal site for quantitative ultrasound assessment because it has a high percentage of trabecular bone that is replaced more often than cortical bone, providing early evidence of metabolic change. also, the calcaneus is fairly flat and parallel, reducing repositioning errors. the method can be applied to children, neonates, and preterm infants, just as well as to adults. some ultrasound devices can be used on the tibia. screening the u.s. preventive services task force (uspstf) recommend that all women 65 years of age or older be screened by bone densitometry. additionally they recommend screening younger women with risk factors. there is insufficient evidence to make recommendations about the intervals for repeated screening and the appropriate age to stop screening. in men the harm versus benefit of screening for osteoporosis is unknown. prescrire states that the need to test for osteoporosis in those who have not had a previous bone fracture is unclear. the international society for clinical densitometry suggest bmd testing for men 70 or older, or those who are indicated for risk equal to that of a 70‑year‑old. a number of tools exist to help determine who is reasonable to test. prevention lifestyle prevention of osteoporosis is in many aspects the inverse of the potentially modifiable risk factors. as tobacco smoking and high alcohol intake have been linked with osteoporosis, smoking cessation and moderation of alcohol intake are commonly recommended as ways to help prevent it. in people with coeliac disease adherence to a gluten-free diet decreases the risk of developing osteoporosis and increases bone density. the diet must ensure optimal calcium intake (of at least one gram daily) and measuring vitamin d levels is recommended, and to take specific supplements if necessary. nutrition studies of the benefits of supplementation with calcium and vitamin d are conflicting, possibly because most studies did not have people with low dietary intakes. a 2018 review by the uspstf found low-quality evidence that the routine use of calcium and vitamin d supplements (or both supplements together) did not reduce the risk of having an osteoporotic fracture in male and female adults living in the community who had no known history of vitamin d deficiency, osteoporosis, or a fracture. the uspstf does not recommend low dose supplementation (less than 1 g of calcium and 400 iu of vitamin d) in postmenopausal women as there does not appear to be a difference in fracture risk. a 2015 review found little data that supplementation of calcium decreases the risk of fractures. while some meta-analyses have found a benefit of vitamin d supplements combined with calcium for fractures, they did not find a benefit of vitamin d supplements (800 iu/day or less) alone. while supplementation does not appear to affect the risk of death, an increased risk of myocardial infarctions kidney stones, and stomach problems is associated with calcium supplementation. vitamin k deficiency is also a risk factor for osteoporotic fractures. the gene gamma-glutamyl carboxylase (ggcx) is dependent on vitamin k. functional polymorphisms in the gene could attribute to variation in bone metabolism and bmd. vitamin k2 is also used as a means of treatment for osteoporosis and the polymorphisms of ggcx could explain the individual variation in the response to treatment of vitamin k. dietary sources of calcium include dairy products, leafy greens, legumes, and beans. there has been conflicting evidence about whether or not dairy is an adequate source of calcium to prevent fractures. the national academy of sciences recommends 1,000 mg of calcium for those aged 19–50, and 1,200 mg for those aged 50 and above. a review of the evidence shows no adverse effect of higher protein intake on bone health. physical exercise there is limited evidence indicating that exercise is helpful in promoting bone health. there is some evidence that physical exercise may be beneficial for bone density in postmenopausal women and lead to a slightly reduced risk of a bone fracture (absolute difference 4%). weight bearing exercise has been found to cause an adaptive response in the skeleton. weight bearing exercise promotes osteoblast activity, protecting bone density. a position statement concluded that increased bone activity and weight-bearing exercises at a young age prevent bone fragility in adults. bicycling and swimming are not considered weight-bearing exercise. neither contribute to slowing bone loss with age, and professional bicycle racing has a negative effect on bone density. low-quality evidence suggests that exercise may reduce pain and improve quality of life of people with vertebral fractures and there is moderate-quality evidence that exercise will likely improve physical performance in individuals with vertebral fractures. physical therapy people with osteoporosis are at higher risk of falls due to poor postural control, muscle weakness, and overall deconditioning. postural control is important to maintaining functional movements such as walking and standing. physical therapy may be an effective way to address postural weakness that may result from vertebral fractures, which are common in people with osteoporosis. physical therapy treatment plans for people with vertebral fractures include balance training, postural correction, trunk and lower extremity muscle strengthening exercises, and moderate-intensity aerobic physical activity. the goal of these interventions are to regain normal spine curvatures, increase spine stability, and improve functional performance. physical therapy interventions were also designed to slow the rate of bone loss through home exercise programs. whole body vibration therapy has also been suggested as a physical therapy intervention. moderate to low-quality evidence indicates that whole body vibration therapy may reduce the risk of falls. there are conflicting reviews as to whether vibration therapy improves bone mineral density. physical therapy can aid in overall prevention in the development of osteoporosis through therapeutic exercise. prescribed amounts of mechanical loading or increased forces on the bones promote bone formation and vascularization in various ways, therefore offering a preventative measure that is not reliant on drugs. specific exercise interacts with the body's hormones and signaling pathways which encourages the maintenance of a healthy skeleton. hormone therapy reduced oestrogen levels increase the risk of osteoporosis, so hormone replacement therapy when women reach the menopause may reduce the incidence of osteoporosis. management lifestyle weight-bearing endurance exercise and/or exercises to strengthen muscles improve bone strength in those with osteoporosis. aerobics, weight bearing, and resistance exercises all maintain or increase bmd in postmenopausal women. fall prevention can help prevent osteoporosis complications. there is some evidence for hip protectors specifically among those who are in care homes. pharmacologic therapy the us national osteoporosis foundation recommends pharmacologic treatment for patients with hip of spine fracture thought to be related to osteoporosis, those with bmd 2.5 sd or more below the young normal mean (t-score -2.5 or below), and those with bmd between 1 and 2.5 sd below normal mean whose 10-year risk, using frax, for hip fracture is equal or more than 3%. bisphosphonates are useful in decreasing the risk of future fractures in those who have already sustained a fracture due to osteoporosis. this benefit is present when taken for three to four years. they do not appear to change the overall risk of death. tentative evidence does not support the use of bisphosphonates as a standard treatment for secondary osteoporosis in children. different bisphosphonates have not been directly compared, therefore it is unknown if one is better than another. fracture risk reduction is between 25 and 70% depending on the bone involved. there are concerns of atypical femoral fractures and osteonecrosis of the jaw with long-term use, but these risks are low. with evidence of little benefit when used for more than three to five years and in light of the potential adverse events, it may be appropriate to stop treatment after this time. one medical organization recommends that after five years of medications by mouth or three years of intravenous medication among those at low risk, bisphosphonate treatment can be stopped. in those at higher risk they recommend up to ten years of medication by mouth or six years of intravenous treatment. the goal of osteoporosis management is to prevent osteoporotic fractures, but for those who have sustained one already it is more urgent to prevent a secondary fracture. that is because patients with a fracture are more likely to experience a recurrent fracture, with marker increase in morbidity and mortality compared. among the five bisphosphonates, no significant differences were found for a secondary fracture for all fracture endpoints combined. that being said, alendronate was identified as the most efficacious for secondary prevention of vertebral and hip fractures while zoledronate showed better performance for nonvertebral non-hip fracture prevention. there is concern that many people do not receive appropriate pharmacological therapy after a low-impact fracture. for those with osteoporosis but who have not had a fracture, evidence does not support a reduction in fracture risk with risedronate or etidronate. alendronate decreases fractures of the spine but does not have any effect on other types of fractures. half stop their medications within a year. when on treatment with bisphosphonates rechecking bone mineral density is not needed. there is tentative evidence of benefit in males with osteoporosis. fluoride supplementation does not appear to be effective in postmenopausal osteoporosis, as even though it increases bone density, it does not decrease the risk of fractures. teriparatide (a recombinant parathyroid hormone) has been shown to be effective in treatment of women with postmenopausal osteoporosis. some evidence also indicates strontium ranelate is effective in decreasing the risk of vertebral and nonvertebral fractures in postmenopausal women with osteoporosis. hormone replacement therapy, while effective for osteoporosis, is only recommended in women who also have menopausal symptoms. it is not recommended for osteoporosis by itself. raloxifene, while effective in decreasing vertebral fractures, does not affect the risk of nonvertebral fracture. and while it reduces the risk of breast cancer, it increases the risk of blood clots and strokes. while denosumab is effective at preventing fractures in women, there is not clear evidence of benefit in males. in hypogonadal men, testosterone has been shown to improve bone quantity and quality, but, as of 2008, no studies evaluated its effect on fracture risk or in men with a normal testosterone levels. calcitonin while once recommended is no longer due to the associated risk of cancer and questionable effect on fracture risk. alendronic acid/colecalciferol can be taken to treat this condition in post-menopausal women. romosozumab (sold under the brand name evenity) is a monoclonal antibody against sclerostin. romosozumab is