Osteoporosis


Article Author:
Joann Porter


Article Editor:
Matthew Varacallo


Editors In Chief:
Alexandra Caley
Sameh Boktor


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Kyle Blair
Trevor Nezwek
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Abbey Smiley
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Daniyal Ameen
Altif Muneeb
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes
Komal Shaheen
Sandeep Sekhon


Updated:
6/4/2019 8:08:32 PM

Introduction

Osteoporosis is defined as low bone mineral density caused by altered bone microstructure ultimately predisposing patients to low-impact, fragility fractures. Osteoporotic fractures lead to a significant decrease in quality of life, with an increased morbidity, mortality, and disability.[1] Over 50% of postmenopausal Caucasian women will have an osteoporotic-related fracture. Only 33% of senior women who have a hip fracture will be able to return to independence. In Caucasian men, the risk of an osteoporotic fracture is 20%, but the one-year mortality in men who have a hip fracture is twice that of women. Black males and females have less osteoporosis than their Caucasian counterparts, but those diagnosed with osteoporosis have similar fracture risks. The aging of the American population is expected to triple the number of osteoporotic fractures. [2][3][4][5]

Etiology

Primary osteoporosis is related to the aging process in conjunction with decreasing sex hormones.  The bones have deterioration in microarchitecture leading to loss of bone mineral density and increased risk of a fracture. Other diseases or their treatments cause secondary osteoporosis. Men are much more likely than women to have secondary osteoporosis. Medications that can lead to secondary osteoporosis include glucocorticoids and anti-epileptics. Other medications such as chemotherapy agents, proton pump inhibitors, and thiazolidines are less well studied but suspected to also contribute to osteoporosis.

Disease states that can cause osteoporosis include hyperparathyroidism, anorexia, malabsorption, hyperthyroidism, or overtreatment of hypothyroidism, chronic renal failure, Cushing, and any disease that can lead to long-term immobilization. Secondary amenorrhea for more than one year from various causes including non-estrogen hormonal therapy, low body weight, and excessive exercise can also lead to rapid loss of bone mass.

Risk factors for osteoporosis include increasing age, a body weight less than 128 pounds, smoking, family history of osteoporosis, white or Asian race, early menopause, low levels of physical activity and a personal history of a fracture from a ground level fall or minor trauma after the age of forty. [6][1]  Patients afflicted with conditions affecting overall mobility level, such as spinal cord injuries (SCI), can experience rapid deterioration of bone mineral density levels within the first 2 weeks following these debilitating injuries. [7]

Epidemiology

Over 200 million people have osteoporosis and the incidence rate increases with age. Over 70% of those over age 80 are affected. It is more common in females than males. In the developed world, 2% to 8% of males and 9% to 38% of females are affected. Worldwide, there are approximately 9 million fractures per year as a result of osteoporosis. [8][9][10]

One in 3 females and 1 in 5 males over the age of 50 will have an osteoporotic fracture. Areas of the world with less Vitamin D through sunlight compared to regions closer to the equator have higher fracture rates in comparison to people living at lower latitudes.

Pathophysiology

Osteoporosis is caused by an imbalance of bone resorption and bone remodeling leading to decreased skeletal mass. In most individuals, bone mass peaks in the third decade, after which bone resorption exceeds bone formation. Failure to reach a normal peak bone mass or acceleration of bone loss can lead to osteoporosis. [1]

Histopathology

Histologic specimens demonstrate markedly thinned trabeculae, decreased osteon size, and enlarged haversian and marrow spaces. [3]

Toxicokinetics

Side effects and costs of treatment are the major considerations when prescribing medications for osteoporosis. It should be noted that intravenous bisphosphonates can be used if a patient is intolerant of oral bisphosphonates before advancing to different treatment options, as they can be tolerated by patients intolerant of the oral dosing.

History and Physical

A comprehensive history and physical includes eliciting potential risk factors attributable to secondary bone loss. A thorough social history also should be obtained with attention to smoking history and chronic alcohol consumption. A family history of osteoporosis also should be noted. The patient should be asked about any prior fractures with focus given to low energy ground level fall mechanisms and any fractures after the age of 40.

The physical exam rarely reveals any changes until osteoporosis is quite advanced. At that point, loss of height and kyphosis is evident from vertebral fractures.

In healthy individuals without risk factors, experts recommend starting to screen women at the age of 65 years of age and men at the age of 70. It should be noted that the United States Preventative Services Task Force did not find sufficient evidence to establish screening for men. Patients with risk factors or a high score on an osteoporosis risk assessment test should be screened sooner.

Women with normal dual-energy x-ray absorptiometry scans do not need follow-up dual-energy x-ray absorptiometry scans as studies have shown that most women with normal scores did not progress to osteoporosis. Using these scans to follow up osteoporosis treatment has rarely led to treatment changes as long as compliance with medications can be assessed in other ways.

Evaluation

Patients with a diagnosis of osteoporosis should have laboratory assessment of their renal and thyroid function, a 25-hydroxyvitamin D and calcium level. The World Health Organization (WHO) has established dual x-ray absorptiometry tests scans of the central skeleton is the best test for assessing bone mineral density.  A dual x-ray absorptiometry scan can be completed in five minutes with minimal radiation exposure. Dual x-ray absorptiometry scans measure all calcified tissue in the path of the scan and specificity is better than sensitivity.

Peripheral dual x-ray absorptiometry tests and ultrasound measure density in bones not at high risk and do not correlate well to the standard dual x-ray absorptiometry scan of the hip and spine. They are not as useful in diagnosis or treatment decisions.

A dual x-ray absorptiometry scan reports a t-score and a z-score. A t-score reflects the difference between the measured bone mineral density and the mean value of bone mineral density in young adults. It is measured in standard deviations. The WHO has defined normal bone mineral density for women as a t-score within one standard deviation of the young adult mean. Scores between negative 1 and negative 2.5 reflect a diagnosis of osteopenia. Scores below negative 2.5 reflect a diagnosis of osteoporosis.

Instead of measuring against a young adult mean, a z-score is the number of standard deviations above or below the age-matched bone mineral density. It is useful when suspecting secondary osteoporosis. A score is less than negative 1.5 warrants a workup for secondary causes of osteoporosis.

The low bone density of the hip has the highest predictive value of future fracture. This is because spine bone density can be falsely elevated due to calcification from degenerative joint disease. Density in the spine can still be useful in younger perimenopausal women without significant degenerative joint disease where the spine can show initial osteoporotic changes before it can be detected in the hip.

A validated tool developed by the World Health Organization is the osteoporosis risk assessment tool which gives a ten-year probability of a major fracture.  It can be used on men or women and takes into account the body mass index, independent risk factors and some causes of secondary osteoporosis. It is most useful in determining which patients with osteopenia need treatment and in determining which patients younger than the age of 50 would benefit from dual x-ray absorptiometry scanning due to high risk of fractures. It does not have utility for patients who are already being treated for osteoporosis. 

Treatment / Management

Recommend lifestyle changes to all patients. Weight-bearing physical activity and exercise that improves balance such as yoga and tai chi should be encouraged. Treatment should be offered to help with both smoking and alcohol cessation. Recommend calcium and Vitamin D3 to all patients, and patients who are vitamin D deficient should have a treatment that raises their levels to be normal. 

Patients with a t-score of negative 2.5 or less should receive treatment. It is also indicated for patients with osteopenia (t-score between negative 1 and negative 2.5) who score on the osteoporosis risk assessment test as having a 3% or higher risk of hip fracture. Patients with a personal history of a fragility fracture can be treated without further testing.

There are multiple pharmacologic treatments available. These agents work through either antiresorptive or anabolic means. In women with known osteoporosis, the recommendations are to start treatment with risedronate, alendronate, zoledronic acid or denosumab to reduce the risk of fracture. These treatments reduce fracture both at vertebral and non-vertebral sites. Bazedoxifene, a selective estrogen receptor modulator combined with conjugated estrogen, has been approved by the FDA for prevention of osteoporosis but not for treatment.

Men should be offered bisphosphonates as first-line therapy.

If patients do not tolerate these medications they can try other medications such as teriparatide. Medications that have only been shown to reduce vertebral fractures, such as raloxifene and ibandronate, should be reserved for patients that cannot tolerate any of the previously mentioned medications. For both groups, any secondary cause should be treated. Use of combination therapy of teriparatide and a bisphosphonate or teriparatide and denosumab in patients with severe osteoporosis and hip and vertebral fractures is worth consideration.

There are no randomized studies regarding monitoring of treatment with follow-up dual x-ray absorptiometry scans. Several studies show that women had reduced fractures with treatment independent of follow-up bone mineral density.     

Recommendations for duration depend on the specific type of medication used for treatment. Some agents such as teriparatide or hormonal-based therapy, need immediate follow-up treatment with another agent or bone mass is lost quickly after discontinuation. There is the ongoing debate about the bisphosphonates with studies underway to determine if drug holidays after five years of therapy or continuous therapy is of most benefit to reduce the fracture.

Pharmacotherapy Options [3]

Pharmacotherapy agents work through either anti-resorptive or anabolic means. Bisphosphonates are the most commonly prescribed medication class. These drugs are divided into non-nitrogen and nitrogen-containing compounds. The latter are considered first-line therapy. The nitrogen-containing compounds inhibit farnesyl pyrophosphate synthase and ultimately inhibit osteoclast resorption and induce osteocyte apoptosis. Common agents include:

  • Alendronate may reduce the rate of hip, spine, and wrist fractures by 50%
  • Risedronate may reduce vertebral and nonvertebral fractures by 40% over three years
  • IV zoledronic acid reduces the rate of spine fractures by 70% and hip fractures by 40% over three years

Other Medication Classes [1]

  • Conjugated estrogen-progestin hormone replacement (HRT)
  • Estrogen-only replacement (ERT)
  • Salmon calcitonin (Miacalcin, Fortical)
  • Selective estrogen receptor modulators (Raloxifene) - Raloxifene is an agonist to estrogen receptors on bone and reduces osteoclast resorption
  • Anabolic (Teriparatide) - Teriparatide is a recombinant form of parathyroid hormone (PTH) that stimulates osteoblasts to produce more bone. Teriparatide is now FDA approved for osteoporosis treatment in males and females
  • RANKL inhibitors (Denosumab) - Denosumab is a monoclonal Ig2 that targets RANKL and inhibits its ability to bind to RANK and results in the inhibition of osteoclast activation

Treatment and Follow-up Considerations [1][11][12][13]

Treatment duration varies depending on the class of medication utilized. Agents such as teriparatide and hormonal-based therapy require immediate follow-up treatment with another agent upon stopping the medication, otherwise, bone mass is rapidly lost. Clinicians also must remain cautious against the prolonged use of uninterrupted bisphosphonate therapy beyond a 3- to 5-year period. Patients should also be made aware of these potentially morbid adverse events, and they should be counseled to seek immediate care if they are experiencing any symptoms of thigh discomfort

Any patient on bisphosphonates for any given time period and presenting with mild thigh discomfort should have the following treatment workup:

  • Educate on the risks of and immediately stop all weight-bearing activity
  • Obtain full-length femur and hip radiographs. Thigh pain may be indicative of an impending pathologic, atypical femur fracture. Attention should be directed to the subtrochanteric and diaphyseal regions of the femur, particularly the lateral cortex which often demonstrates evidence of periosteal reaction
  • Immediately discontinue bisphosphonate use
  • Refer to an orthopedic surgeon for prophylactic surgical fixation

Enhancing Healthcare Team Outcomes

Osteoporosis is a major public health problem affecting millions of elderly individuals. Besides causing fractures, the disorder leads to severe psychosocial and financial consequences for the patient. The condition has many risk factors and is best managed by a multidisciplinary team of healthcare workers. Patient education is vital as many patients are unaware of the serious consequences of the disorder. Early prevention can help reduce the high morbidity. Patients should be urged to modify their lifestyle and remain compliant with the medications prescribed. In addition, the patient should be urged to quit smoking and abstain from alcohol. The outcomes in patients with osteoporosis are guarded. Close to 250,000 hip fractures occur each year as a result of osteoporosis, and once admitted, there is a mortality rate exceeding 20%. Men with a hip fracture, in general, have a much higher mortality than women. Even after recovery, many patients lose their independence and close to 30% require nursing home care. Full recovery rarely occurs and the overall quality of life is poor. Many patients develop secondary complications like pressure sores, deep vein thrombosis, and nosocomial infections.[14][15]


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Osteoporosis - Questions

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Your patient has osteoporosis. To treat this condition, you will teach the patient to consume foods from which of the following groups?



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Which of the following is not associated with osteoporosis?



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Which of the following might be indicated for a 68-year-old female developing osteoporosis?



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Which of the following laboratory values is most consistent with osteoporosis in a 69-year-old female?



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Which of the following would not help prevent osteoporosis?



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Which of the following is a risk factor for osteoporosis?



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A 66-year-old woman is taking calcium supplements to reduce her risk of osteoporosis. What other supplementation may be needed in this patient?



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Which is not a risk factor for the development of osteoporosis?



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Which of the following does not prevent osteoporosis?



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Which is the most important instruction for an osteoporosis patient discharged from an acute care facility?



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Select the incorrect statement about osteoporosis.



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Which of the below exercises is best for the preservation of bone mass density in patients with osteoporosis?



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Which of the following is not true about osteoporosis?



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Which of the following female populations has a high risk of osteoporosis?



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Which of the following medications is not associated with osteoporosis?



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Which of the following findings is most consistent with osteoporosis?



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A 75-year-old female has a wrist fracture and is concerned about future fractures. Which of the following is not a risk factor?



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Which medication is not indicated for the treatment of osteoporosis?



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Which of the following is a non-modifiable risk factor for the development of osteoporosis?



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Select the option that is not an osteoporosis risk factor.



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A 75-year-old thin female is hospitalized for pain control secondary to a non-traumatic thoracic spine compression fracture. What is the most likely cause of the compression fracture?



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An elderly female patient has acute onset of posterior thoracic pain. There was no injury, and the pain is sharp and non-radiating. There is no shortness of breath or change with exercise. A dual x-ray absorptiometry (DEXA) score three years ago showed a t-score of negative two. Select the most likely disease process.



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A 75-year-old female complains of sudden onset of mid-back pain worsening when going from sitting to standing. Which historical fact would be of most help in determining the cause of the pain?



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Select the true statement about treatment of osteoporosis.



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Which of the following is not a risk factor for osteoporotic fractures?



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Select the MOST common site for osteoporosis-associated fractures.



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Which of the following is the World Health Organization's (WHO) definition of osteoporosis?



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A 65-year-old female has a hip fracture and is diagnosed with osteoporosis. Laboratories show a calcium of 8.6 mg/dL, phosphate 2.9 mg/dL, creatinine 0.9 mg/dL, and 25-hydroxyvitamin D levels of 20 ng/mL (normal >30 ng/mL). A dual x-ray absorptiometry scan shows a t-score of negative 3. Which of the following is the best initial therapy for this patient?



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When bone resorption is greater than bone formation which of the following results?



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Which of the following is not a risk factor for osteoporosis?



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Caucasian females are more at risk for which of the following fractures?



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What is the value of urinary N-telopeptide?



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A 79-year-old female presents with a complaint of chronic and progressive mid-back pain for several months but no other symptoms. Spinal x-rays reveal two compression fractures of the T10 vertebral body. Calcium, phosphate and alkaline phosphatase levels are within the reference range. Histological examination of the affected vertebral bone most likely will reveal which of the following?



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Which is the least common fracture site in men with osteoporosis?



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What is the best method to diagnose osteoporosis?



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What is the t-score for which osteoporosis is diagnosed?



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What medication has been shown to reduce hip fractures in osteoporosis patients?



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What condition causes a decrease in bone density that makes them weak and thin?



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A 50-year-old postmenopausal female is being placed on a regimen of estrogen hormone replacement therapy and calcitonin for osteoporosis prophylaxis. She also has been instructed to initiate weight-bearing exercise as an adjunct. Which of the following is true about this treatment plan?



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A 76-year-old female with known osteopenia presents to you for a checkup. She reports she is intolerant of daily alendronate and raloxifene. Her last dual-energy x-ray absorptiometry (DEXA) was obtained 15 months ago. She is otherwise healthy. Her risk factors include a personal history of fracture from a ground level fall and her weight of 123 pounds. You order a repeat DEXA scan. Her lumbar spine T-score is -2.16, and her hip T-score is -2.49. Her lumbar spine T-score has decreased by 3.2%, and her hip has decreased by 3.8%. What is your recommendation?



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A 70-year-old female with a diagnosis of osteoporosis presents to the clinic after a ground level fall resulting in a femur fracture. She has been on alendronate for the last 3 years and compliant with therapy. Her vitamin D levels are normal, and she takes calcium and vitamin D daily. She continues to smoke and has been advised to quit. Her body mass index is below normal. What should be recommended?



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Osteoporosis accounts for what percentage of spine and hip fractures in older women?



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A patient presents with a diagnosis of primary osteoporosis. What is the cause of this illness?



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In general, when do osteoporotic fractures in men occur?



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At what age do osteoporotic fractures in men usually peak?



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Which of the following is not a risk factor for a secondary fracture in men with osteoporosis?



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In an otherwise healthy male, the Endocrine Society recommends screening for osteoporosis in men at what age?



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It is time for a daily impromptu student quiz. One of the students picks "osteoporosis" as the topic. Which of the following is a correct student response? Select all that apply.



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Osteoporosis - References

References

Varacallo MA,Fox EJ, Osteoporosis and its complications. The Medical clinics of North America. 2014 Jul     [PubMed]
Varacallo MA,Fox EJ,Paul EM,Hassenbein SE,Warlow PM, Patients' response toward an automated orthopedic osteoporosis intervention program. Geriatric orthopaedic surgery & rehabilitation. 2013 Sep     [PubMed]
Varacallo M,Pizzutillo P, Osteopenia . 2018 Jan     [PubMed]
Kanis JA,Johansson H,Harvey NC,McCloskey EV, A brief history of FRAX. Archives of osteoporosis. 2018 Oct 31     [PubMed]
Walzak LC,Loken Thornton W, The role of illness burden in theory of mind performance among older adults. Experimental aging research. 2018 Oct-Dec     [PubMed]
Greenstein AS,Gorczyca JT, Orthopedic Surgery and the Geriatric Patient. Clinics in geriatric medicine. 2019 Feb     [PubMed]
Varacallo M,Pizzutillo P, Osteoporosis, Spinal Cord Injury . 2018 Jan     [PubMed]
Prince RL,Lewis JR,Lim WH,Wong G,Wilson KE,Khoo BC,Zhu K,Kiel DP,Schousboe JT, Adding Lateral Spine Imaging for Vertebral Fractures to Densitometric Screening: Improving Ascertainment of Patients at High Risk of Incident Osteoporotic Fractures. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2018 Nov 5     [PubMed]
Rachner TD,Hofbauer L,Göbel A,Tsourdi E, Novel therapies in osteoporosis: PTH-related peptide analogues and inhibitors of sclerostin. Journal of molecular endocrinology. 2018 Sep 1     [PubMed]
Khadka B,Tiwari ML,Gautam R,Timalsina B,Pathak NP,Kharel K,Sharma S,Acharya D, Correlates of Biochemical Markers of Bone turnover among Post-Menopausal Women. JNMA; journal of the Nepal Medical Association. 2018 Jul-Aug     [PubMed]
Jiang SY,Kaufman DJ,Chien BY,Longoria M,Shachter R,Bishop JA, Prophylactic Fixation Can Be Cost-effective in Preventing a Contralateral Bisphosphonate-associated Femur Fracture. Clinical orthopaedics and related research. 2018 Oct 26     [PubMed]
Larsen MS,Schmal H, The enigma of atypical femoral fractures: A summary of current knowledge. EFORT open reviews. 2018 Sep     [PubMed]
Lewiecki EM, New and emerging concepts in the use of denosumab for the treatment of osteoporosis. Therapeutic advances in musculoskeletal disease. 2018 Nov     [PubMed]
Lewiecki EM,Bilezikian JP,Giangregorio L,Greenspan SL,Khosla S,Kostenuik P,Krohn K,McClung MR,Miller PD,Pacifici R, Proceedings of the 2018 Santa Fe Bone Symposium: Advances in the Management of Osteoporosis. Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry. 2018 Sep 22     [PubMed]
Bartosch P,McGuigan FE,Akesson KE, Progression of frailty and prevalence of osteoporosis in a community cohort of older women-a 10-year longitudinal study. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2018 Oct     [PubMed]

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