Osteoporosis in Elderly Patients


Age

Female sex

Low body-mass index

Previous fragility fracture, particularly of the hip, wrist and spine

Parental history of hip fracture

Glucocorticoid treatment (≥5 mg prednisolone daily or equivalent for 3 months or more)

Current smoking

Alcohol intake of three or more units daily

Premature menopause

Vitamin D deficiency

Reduced calcium intake

Drugs

Osteoporosis -related pathologies (see Table 3.2)

Organ transplant




3.3.1 BMD


Several studies have demonstrated that the reduction of a single standard deviation in BMD corresponds to an increase in fracture risk of 1.5–3-fold. The predictive power of BMD is similar to that of hypertension in the case of stroke [1]. However, fracture risk is not only related to BMD, but depends also on a number of other factors and, consequently, T-score values alone are not sufficient to define probability of fracture and determine when a patient needs to be treated [9]. Moreover the majority of fractures occur in osteopenic patients (T scores of −2.5 to −1.0) [10].


3.3.2 Age


Age contributes, independently of BMD, to fracture risk; therefore, in the presence of the same BMD score, the risk of fracture will be higher for the elderly than for the young [9, 11]. Another major problem regarding the elderly is their reduced muscular functionality. This is an age-related condition, but it is often exasperated by deficient nutrition and reduced mobility. Weakness is one of the five items that define the frailty syndrome as proposed by Fried and colleagues, the others being unintentional weight loss, self-reported exhaustion, slow walking speed and low physical activity [12]. Moreover, the “frail phenotype” is associated with a very high risk of falls leading to fracture [13].


3.3.3 Previous Fractures


The presence of a previous fracture, regardless of its site, is an important risk factor for further fractures and is independent of BMD. The most prognostic fractures are those of the vertebrae, hip, humerus, and wrist. Moreover, risk of further fracture increases with the number of previous fractures: patients with three or more previous fractures have a ten-times greater risk of fracture than patients who have never suffered from fractures [1].


3.3.4 Family History of Fracture


Family history influences fracture risk independently of BMD. In particular, parental hip-fracture is significantly related to higher risk of hip fractures in offspring and, to a lesser extent, of all other kinds of osteoporotic fractures [1].


3.3.5 Comorbidities


A large range of pathologies are related to increased rates of fracture risk (Table 3.2). In some cases, the increased fracture risk is caused through a reduction in BMD, but often other mechanisms are involved: chronic inflammation, alteration of bone quality, general impairment of health conditions, reduction of mobility, sarcopenia, with higher risk of falls and other complications. Vitamin-D deficiency, which often coexists with this pathology, is another negative factor [1].


Table 3.2
Osteoporosis-related pathologies






























Endocrine disorders

Hypogonadism

Hypercortisolism

Hyperparathyroidism

Hyperthyroidism

Hyperprolactinaemia

Diabetes mellitus types I and II

Acromegaly

GH deficiency

Haematological disorders

Myelo-lymphoproliferative diseases

Multiple myeloma and monoclonal gammopathies

Systemic mastocytosis

Thalassemia

Sickle-cell anemia

Haemophilia

Gastrointestinal disorders

Chronic liver disease

Primary biliary cirrhosis

Celiac disease

Chronic inflammatory bowel diseases

Gastro-intestinal resection

Gastric bypass

Lactose intolerance

Intestinal malabsorption

Pancreatic insufficiency

Rheumatoid disorders

Rheumatoid arthritis

LES

Ankylosing spondylitis

Psoriatic arthritis

Scleroderma

Other forms of connectivitis

Renal disorders

Renal idiopathic hypercalciuria

Renal tubular acidosis

Chronic renal failure

Neurologic disorders

Parkinson disease

Multiple sclerosis

Paraplegia

Outcomes of stroke

Muscular dystrophies

Genetic disorders

Osteogenesis imperfecta

Ehlers-Danlos syndrome

Gaucher syndrome

Glycogenosis

Hypophosphatasia

Hemochromatosis

Homocystinuria

Cystic fibrosis

Marfan syndrome

Menkes syndrome

Porphyria

Riley-Day syndrome

Other pathologies

Chronic obstructive pulmonary disease

Anorexia nervosa

AIDS/HIV

Amyloidosis

Sarcoidosis

Depression


3.3.6 Drugs


Several drugs increase fracture risk. The most important class of drugs are glucocorticoids that have a negative effect on bone, causing rapid bone-quality loss and BMD depletion. Among the more recent classes of drugs, hormone-blockade treatments (aromatase inhibitors for women operated for breast cancer and GnRH agonists for men with prostate cancer) also lead to a reduction of BMD but at a slower rate. Other drugs involved are SSRI, PPI, H2 inhibitors, anticonvulsants, loop diuretics, anticoagulants, excess of thyroid hormones and antiretroviral treatment.


3.3.7 Assessment of Fracture Risk


Although BMD acts as the cornerstone when diagnosing osteoporosis, as mentioned above, the use of BMD alone does not suffice to identify an intervention threshold. This is why a large number of scores are generated in order to better identify fracture risks; the most widely used assessment tool is FRAX®. This is a web-based algorithm (​www.​shef.​ac.​uk/​FRAX) which calculates the 10-year probability of a major fracture (hip, clinical spine, humerus or wrist) and a 10-year hip-fracture probability. Fracture risk is calculated on the basis of age, body mass index and dichotomised risk factors including prior fragility fracture, parental hip-fracture history, current tobacco smoking, long-term use of oral glucocorticoids, rheumatoid arthritis, other causes of secondary osteoporosis and alcohol consumption. Femoral-neck BMD may be inserted to improve fracture risk prediction. Fracture probability differs considerably in different countries around the world; that is why FRAX is calibrated to match those countries where the epidemiology rates for fracture and death are known [14].

FRAX has some limitations: it does not take into account dose responses for several risk factors, for example glucocorticoid exposure, smoking, alcohol intake and the number of previous fractures [15]. A further limitation is that the FRAX algorithm uses only T-scores for the femoral neck and does not take T-scores of the lumbar spine into account when, at times, there is discordance between these two measurement sites [16].

Despite the fact that international literature has demonstrated the validity of these instruments when evaluating risk of fracture, the intervention thresholds for osteoporosis currently depend on regional treatment and reimbursement policies which are increasingly based on cost-effectiveness evaluations [17].



3.4 Diagnosis


There is no universally accepted population-screening policy in Europe for the recognition of patients with osteoporosis or those at high risk of fracture. In the absence of such a policy, patients are identified opportunistically using a case-finding strategy based on previous fragility fractures (see Chap. 12) or on the presence of significant risk factors [2].


3.4.1 Instrumental Diagnosis


Bone Mineral Density (BMD) may be evaluated by several techniques generally described as bone densitometry. Densitometry permits accurate measurement of bone mass, which is the best predictor of osteoporotic fracture risk. The result is expressed as a T-score, which is the difference between the subject’s BMD value and the mean BMD value for healthy young adults (peak bone mass) of the same sex, expressed in standard deviations (SD). BMD can also be expressed by comparing the average value for subjects of the same age and sex (Z-score). The threshold required to diagnose the presence of osteoporosis, according to WHO, is a T-score < −2.5 SD.


Dual X-ray Absorptiometry (DXA)

this is, at present, the technique preferred for bone-mass evaluation to enable the diagnosis of osteoporosis, prediction of fracture risk and follow-up monitoring. The technique uses X-Rays of two different energies, which allow the subtraction of soft tissue absorption and the estimate of calcium content of the bone. When projected onto a surface this gives a parameter called Bone Mineral Density (BMD g/cm2), from which Bone Mineral Content (BMC, g/cm3) may be inferred. In general, measurement at a particular site provides a more accurate estimate of fracture risk for that site. Since the most clinically relevant osteoporotic fractures occur in the spine and in the hip, the most frequently measured sites are the lumbar spine and proximal femur. However, there are a number of technical limitations to the application of DXA to diagnosis. For example, the presence of osteomalacia will underestimate total bone matrix because of decreased bone mineralisation while, on the other hand, osteoarthrosis or osteoarthritis of the spine or hip will contribute to density but not to skeletal-strength [2]. In the latter case, the specific site involved must be excluded from the analysis; at least two lumbar vertebrae must be evaluated so that the densitometry result may be considered reasonably accurate. For this reason, femoral densitometric evaluation is probably preferable after the age of 65. Recently some software has been developed to enable DXA to measure, not only BMD, but also some of the geometrical parameters related to bone strength, such as HSA (hip structure analysis) and TBS (Trabecular Bone Score). TBS processes the degree of inhomogeneity of the spinal densitometry scan, thus providing indirect information regarding trabecular microarchitecture. Although this device has been approved by the FDA, its everyday use in clinical practice is still limited.


Quantitative Computerized Tomography QCT

this technique, because it is able to separate the trabecular BMD from the cortical BMD, permits total and local volumetric BMD (g/cm3) measurements at both vertebrae and femur levels. However, this method exposes patients to high radiation dose levels (about 100 μSv). As a technique, DXA is usually preferred to QCT because of its accuracy, shorter scan times, more stable calibration, lower radiation dose and lower costs.


Quantitative Ultrasound (QUS)

This technique provides two parameters (speed and attenuation) which are indirect indicators of bone mass and structural integrity; it is used mainly to carry out measurements in two sites, the phalanges and the calcaneus. It has been demonstrated that ultrasound parameters are capable of predicting risk of osteoporotic fractures (femoral and vertebral) no less accurately than lumbar or femoral DXA, both in post-menopausal women and in men, but this technique does not provide direct bone-density measurements. Discordant results between ultrasonographic and DXA evaluations are neither surprising nor infrequent and they do not necessarily indicate an error, but rather, that the QUS parameters are independent predictors of fracture risk influenced by other characteristics of the bone tissue. However, this does mean that QUS cannot be used for the diagnoses of osteoporosis based on WHO criteria. QUS can be useful when it is not possible to estimate a lumbar or femoral BMD with DXA and may be recommended for epidemiological investigations and first-level screening, considering its relatively low cost, easy transportability and absence of radiation.


3.4.2 X-ray of the Dorsal and Lumbar Spine


The presence of a non-traumatic vertebral fracture indicates a condition of skeletal fragility, regardless of BMD, and is a strong indicator of the need to start treatment in order to reduce risks of further fractures. Since most vertebral fractures are mild and asymptomatic, the use of diagnostic imaging is the only way to diagnose them. Vertebral fractures are defined, applying Genant’s semi-quantitative method (SQ), as a 20 % reduction in one vertebral body height.


3.4.3 Laboratory Tests


Laboratory tests are an indispensable step in the diagnosis of osteoporosis because they can distinguish between this pathology and other metabolic diseases of the skeleton, which may present a clinical picture similar to that of osteoporosis. Moreover, they can identify possible causal factors, permitting the diagnosis of secondary osteoporosis and suggesting an aetiological treatment where one exists. First-level tests are: blood count, protein electrophoresis, serum-calcium and phosphorus levels, total alkaline phosphatase, creatinine, the erythrocyte sedimentation rate and 24 h urinary calcium. Normal results for these tests exclude 90 % of other diseases or forms of secondary osteoporosis. Sometimes it is necessary to perform second-level tests too, such as: ionised calcium, TSH, PTH, serum 25-OH-vitamin D, cortisol after a suppression test with 1 mg of dexamethasone, total testosterone in males, serum and/or urinary immunofixation for anti-transglutaminase antibodies and specific tests for associated diseases.

The specific markers of bone turnover, detectable in serum and/or urine, are divided into bone-formation (bone isoenzyme of alkaline phosphatase, osteocalcin, type I procollagen propeptide) and bone-resorption markers (pyridinoline, deoxypyridinoline, N or C telopeptides of collagen type I). In adult subjects, the increase in bone turnover markers indicates accelerated bone loss or the existence of other primary or secondary skeletal disorders (osteomalacia, Paget’s disease, skeletal localisations of cancer). Markers are overall indices of skeletal remodelling and they may be useful when monitoring the efficacy of and adherence to a therapy. However, these markers are characterised by broad biological variability so, at present, they cannot be used for routine clinical evaluations.


3.5 Treatment



3.5.1 General Management


Immobility is one of the most important causes of bone loss and should be avoided wherever possible. Weight-bearing exercises are optimal for skeletal health and are therefore an important component of the management of patients with osteoporosis [18].


Prevention of Falls

Risk factors for falls include history of fracture/falls, dizziness and orthostatic hypotension visual impairment, gait deficits, urinary incontinence, chronic musculoskeletal pain, depression, functional and cognitive impairment, low body mass index, female sex, erectile dysfunction (in male adults), and people aged over 80 [19]. Some of these factors are modifiable: reduced visual acuity can be corrected, medication that may diminish awareness and/or balance can be reduced or stopped and modifications to the home environment can be performed (slippery floors can be corrected, mats can be fixed or removed, lighting improved, handrails placed in bathrooms etc.) [20]. A programme of exercises may prevent falls by improving confidence and coordination and by preserving muscle strength but there is no consensus around the most suitable programme for the ‘oldest old’ [20, 21].


Vitamin D

Vitamin D is involved in the intestinal absorption of calcium and phosphorus and is necessary for the mineralisation of bone and the maintenance of muscle, but it also has numerous beneficial effects on other organs. Most Vitamin D is synthesised in the skin during exposure to the sun but, as this capacity is reduced in older people, they produce lower amounts of vitamin D; moreover, they also tend to expose their skin less than younger adults. Thus, the majority of older people suffer from hypovitaminosis D [22]. Threshold values for vitamin D are presented below in Table 3.3. Several trials have demonstrated lower fracture risk in patients having a plasma concentration of 25-hydroxy-vitamin D (25-OH-D) of at least 60 nmol/L compared to those having levels below 30 nmol/L [23]. Moreover, there is growing evidence that vitamin D supplementation has beneficial effects on other systems, in addition to the skeleton. It has been demonstrated that improvement of 25-OH-D levels leads to a lower incidence of falls in older people; other trials have demonstrated that vitamin D supplementation is associated with a reduction in all-cause mortality [24]. The Recommended Nutrient Intakes (RNI) are 800 IU of vitamin D per day in men and women over 50 [2]. Intakes of at least 800 IU of vitamin D can be recommended in the general management of patients with osteoporosis, especially in patients receiving bone protective therapy [25]. Considering that hypovitaminosis D is epidemic among the elderly, there is probably no strong necessity to measure circulating levels of 25-OH-D in patients with high fracture risk [22]. Vitamin D supplementation should start as soon as possible, and it should precede the administration of any drug used to treat osteoporosis [25]. Since the inactive form of vitamin D (cholecalciferol) is stored in fat tissue, it is sensible to saturate the stores with repeated small loading doses and then to continue with maintenance doses.
Aug 29, 2017 | Posted by in ORTHOPEDIC | Comments Off on Osteoporosis in Elderly Patients
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