4.7 Osteoporosis

Osteoporosis affects an estimated 75 million people in Europe, the USA, and Japan combined (1). It is a preventable and a treatable condition, yet many patients with fractures remain unrecognized and untreated.

Definitions for osteoporosis have usually been conceptual, and so difficult to relate to individual patients. An example was produced by a Consensus Development Conference (1) as ‘a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration with a consequent increase in bone fragility and susceptibility to fracture’. This definition is elegant but difficult to apply to an individual patient. An operational definition of osteoporosis has been proposed by a Working Group of the WHO (2). This defines osteoporosis by the patient’s bone mineral density (BMD) in relation to the mean value in normal, young subjects. Specifically, osteoporosis is a value for BMD level equal to or less than 2.5 SD below the mean value in young subjects (T score ≤ 2.5) (Fig. 4.7.1). This definition is useful as an entry criterion to a clinical trial or as a tool to study the epidemiology of osteoporosis but it has limitations in clinical practice. It elevates a risk factor for fracture to the status of a diagnostic criterion, it ignores the importance of other determinants of bone strength (3), it ignores higher fracture risk associated with a certain level of BMD in older women, and it does not specify the technique or the site at which BMD should be measured. Bone density results can also be compared to the mean value in normal subjects of the same age (Z score). A Z score below 0.67 would indicate a value in the lowest 25% of the reference range, a level indicating a high lifetime risk of fracture. A Z score below 2 would indicate a value in the lowest 2.5% of the reference range, a level likely to be associated with a high risk factor for osteoporosis.

It is now possible to determine individuals’ risk of osteoporosis using a combination of bone mineral density and clinical risk factors as proposed by a WHO working group (4). A prediction algorithm is available (FRAX, which allows estimation of 10-year risk) and treatment guidance may be based on this (http://www.shef.ac.uk/FRAX).

The commonest osteoporosis-related fractures are the proximal femur (hip), vertebrae (spine), and distal forearm (wrist). Hip fracture rate increases exponentially with age and is three times more common in women than men. About 50% of hip fractures occur after age 80 years. There is an excess mortality of 18% following a hip fracture. Vertebral fractures are asymptomatic in over half of cases, and so their epidemiology is more difficult to define. Morphometric approaches have been applied to large population samples. Up to 25% of women over age 50 years have vertebral fractures and the prevalence in men is similar. Most vertebral fractures in women are a consequence of mild-to-moderate trauma, but in men almost half result from severe trauma. Wrist fracture incidence increases at the time of the menopause but reaches a plateau after age 70 years. There is no increase with age in men and 85% of wrist fractures occur in women. This plateau may be explained by a cessation of bone loss after age 70 years at the wrist or to a different way of falling in the elderly. These fractures carry a large cost to the Health Service, £1.7 billion in the UK. With the ageing of the population (and a secular increase in age-specific fracture incidence) the burden will increase in the future.

Osteoporosis-related fractures result from a combination of decreased BMD and a deterioration in bone microarchitecture. A BMD below average for age can be considered a consequence of inadequate accumulation of bone in young adult life (low peak bone mass) or of excessive rates of bone loss. The microarchitectural changes occur in parallel with the bone loss but will be considered separately.

The increase in bone mass that occurs during childhood and puberty results from a combination of growth of bone at the endplates (endochondral bone formation) and of change in bone shape (modelling) (5). The rapid increase in bone mass at puberty is associated with an increase in sex hormone levels and the closure of the growth plates. Within 3 years of menarche, there is little further increase in bone mass. The small increase in BMD over the next 5–15 years is referred to as ‘consolidation’. The resulting peak bone mass is achieved by age 20–30 years old (6).

Genetic factors are the main determinants of peak bone mass (7). This has been shown by studies made on twins or on mother–daughter pairs. Hereditability appears to account for about 50–85% of the variance in bone mass, depending on the skeletal site. It is likely that several genes regulate bone mass, each with a modest effect, and likely candidates include the genes for type I collagen (COL1A1) and for the lipoprotein related protein (LRP5). The nongenetic factors include low calcium intake during childhood, low body weight at maturity and at 1 year of life, sedentary lifestyle, and delayed puberty. Each of these results in decreased bone mass.

Bone loss occurs in the postmenopausal woman as a result of an increase in the rate of bone remodelling and an imbalance between the activity of osteoclasts and osteoblasts. Bone remodelling occurs at discrete sites within the skeleton and proceeds in an orderly fashion with bone resorption always being followed by bone formation, a phenomenon referred to as ‘coupling’. In cortical and cancellous bone the sequence of bone remodelling is similar (8). The quiescent bone surface is converted to activity (origination) and the osteoclasts resorb bone (progression) forming a cutting cone (cortical bone) or a trench (cancellous bone). The osteoblasts synthesize bone matrix which subsequently mineralizes. The sequence takes up to 8 months. If the processes of bone resorption and bone formation are not matched then there is ‘remodelling imbalance’. In postmenopausal women, this imbalance is magnified by the increase in the rate of initiation of new bone remodelling cycles (activation frequency).

Remodelling imbalance results in irreversible bone loss. There are two other causes of irreversible bone loss, referred to as ‘remodelling errors’. First is excavation of overlarge haversian spaces in cortical bone (9). Radial infilling is regulated by signals from the outermost osteocytes and is generally no more than 90 μm. Hence, large external diameters, which may simply occur randomly, lead to large central haversian canals, which then accumulate with age, leading to increased cortical porosity. In a similar way, osteoclast penetration of trabecular plates, or severing of trabecular beams, removes the scaffolding needed for osteoblastic replacement of resorbed bone. In both ways random remodelling errors tend to reduce both cancellous and cortical bone density and structural integrity.

Bone loss in the postmenopausal woman occurs in two phases (10). There is a phase of rapid bone loss that lasts for 5 years (about 3% per year in the spine). Subsequently, there is lower bone loss that is more generalized (about 0.5% per year at many sites). This slower phase of bone loss affects men, starting at about age 55 years. The rapid phase of bone loss in women is caused by oestrogen deficiency. The circulating level of oestradiol decreases by 90% at the time of the menopause. This bone loss can be prevented by the administration of oestrogen and progestins to the postmenopausal woman. It has been estimated that this rapid phase of bone loss contributes 50% to the spinal bone loss across life in women. The main effect of oestrogen deficiency is on bone, where it increases activation frequency, and may contribute to the remodelling imbalance. Oestrogen deficiency may increase bone resorption by stimulating the synthesis of RANKL by osteoblasts (or their precursors). RANKL binds to its receptor RANK on the osteoclast and promotes differentiation to osteoclasts, increases osteoclast activity and inhibits osteoclast apoptosis. Oestrogen deficiency also increases the apoptosis of osteoblasts and osteocytes.

Oestrogen deficiency may be a determinant of bone loss in men (11). Decreased BMD has been reported in men with an inactivating mutation of the genes for the oestrogen receptor or for aromatase (the enzyme that converts androgens to oestrogens). In older men, oestrogen levels correlate more closely with BMD than testosterone levels. In men with osteoporosis, oestradiol (but not testosterone) levels have been reported to be decreased.

The slow phase of bone loss is attributed to age-related factors such as an increase in parathyroid hormone (PTH) levels (Fig. 4.7.2) and to osteoblast senescence. An increase in PTH levels (and action) occurs in both men and women with ageing. PTH levels correlate with those of biochemical markers of bone turnover and both may be returned to those found in young adults by the intravenous infusion of calcium. The increase in PTH results from decreased renal calcium reabsorption and decreased intestinal calcium absorption. The latter may result from vitamin D deficiency (e.g. in the housebound elderly), decreased 1α-hydroxylase activity in the kidney resulting in decreased synthesis of 1,25-dihydroxyvitamin D, or resistance to vitamin D. Whatever the cause, a diet high in calcium returns both PTH and bone turnover markers to levels found in healthy young adults. It has been proposed that the age-related increase in PTH could result from indirect effects of oestrogen deficiency (10). This proposal is based on the following evidence. In older women treated with oestrogen, (1) there is a decrease in bone turnover markers and PTH levels; (2) there is an increase in calcium absorption, possibly mediated by an increase in 1,25-dihydroxyvitamin D; (3) there is an increase in the PTH-independent calcium reabsorption in the kidney; and (4) there is a decrease in the parathyroid secretory reserve.

A number of diseases and drugs are clearly related to accelerated bone loss (Box 4.7.1). Their effects are superimposed on those described above. Thus, a patient starting on corticosteroid therapy is more likely to have an osteoporosis-related fracture if she has low BMD resulting from low peak bone mass and the accelerated bone loss of the menopause.

In a woman presenting with osteoporosis at age 70 years it is often possible to identify several reasons for the low BMD (Fig. 4.7.3). Some of these may be identified from history taking (early menopause, drugs that accelerate bone loss), but some cannot be identified in retrospect (low peak bone mass and rapid losers).

Bone geometry has a major effect on fracture risk. One example is hip axis length, the distance from the lateral surface of the trochanter to the inner surface of the acetabulum, along the axis of the femoral neck. Short hip axis length results in an architecturally stronger structure for any given bone density. This is probably the reason why Japanese and other Orientals have about half the hip fracture rate of Caucasians, despite similar bone density values.

Fatigue damage consists of ultramicroscopic rents in the basic bony material, resulting from the inevitable bending that occurs when a structural member is loaded. Fatigue damage is the principal cause of failure in mechanical engineering structures; its prevention is the responsibility of the remodelling apparatus which detects and removes fatigue-damaged bone. Fractures related to fatigue damage occur whenever the damage occurs faster than remodelling can repair it or whenever the remodelling apparatus is defective. March fractures and the fractures of radiation necrosis are well-recognized examples of fractures due to these two mechanisms.

Bone structures loaded vertically, such as the vertebral bodies and femoral and tibial metaphyses, derive a substantial portion of their structural strength from a system of horizontal, cross-bracing trabeculae which support the vertical elements and limit lateral bowing and consequent snapping under vertical loading. Severance of such trabecular connections is known to occur preferentially in postmenopausal women and is considered to be an important reason for the large female/male preponderance of low-trauma vertebral fractures.

A number of risk factors have been identified for osteoporosis (Box 4.7.1). Bone loss can be stopped, or reversed, if risk factors such as primary hyperparathyroidism (see Chapter 4.3) are identified and treated. The patient who presents with a vertebral fracture and low BMD is likely to have had one of four causes (Fig. 4.7.3). It is impossible to know the importance of peak bone mass and the rate of bone loss in retrospect. Questions can be asked about early menopause and about the drugs and diseases known to accelerate bone loss. We usually assess risk factors by administering a questionnaire before first attendance at the clinic, by carrying out a limited biochemical work-up before the clinic visit (Box 4.7.2), and, after the clinical, evaluation exploring alternative diagnoses.

A maternal history of hip fracture increases the risk of hip fracture in an individual.

Late-onset forms (e.g. Sillence type I) may present with vertebral fracture. The clinical clues are the blue sclerae, hypermobile joints, lax skin, cardiac murmurs, and deafness (see Chapter 4.11).

Smoking results in lower oestrogen levels and early menopause, and smokers often have a slender stature (see below). Chronic lung disease is associated with chronic respiratory acidosis and decreased physical activity.

The relationship between alcohol and bone loss is complex (and there may even be a protective effect at a low level of intake) (12). Alcoholism results in low BMD because of poor nutrition and pseudo-Cushing’s syndrome, and a direct suppressive effect of alcohol on osteoblasts. Fractures result from the increased propensity to fall.

Athletes have high BMD. However, bone loss only results from complete immobilization (or space flight). The bone loss after paralysis (e.g. stroke) is regional.

This is a risk factor for fracture through decreased oestrogen production from adrenal androgens (in adipose tissue) and through decreased padding (to cushion a fall). Women with hip fracture weigh about 8 kg less than the average woman.

Low dietary calcium and high dietary sodium are considered risk factors for osteoporosis. Calcium requirement increases during growth and in the postmenopausal period. A postmenopausal woman should take 1500 mg/day of calcium.

Ultraviolet light (UVB) acts on the skin as the main source of vitamin D (see Chapter 4.10). The housebound are liable to vitamin D insufficiency. This does not result in clinical osteomalacia, but the decreased calcium absorption (see above) results in secondary hyperparathyroidism.

A menopause before the age of 45 years is associated with increased risk of fracture. A menopause before the age of 40 years is often associated with some endocrine cause and should be investigated further.

A late onset of the menarche and periods of amenorrhoea of any cause, e.g. exercise related, are associated with decreased bone mass later in life.

This is associated with bone loss and increased risk of fracture. The bone loss is probably irreversible after 4 years of amenorrhoea. The mechanism of the bone loss is not just oestrogen deficiency. The diet is low in calcium and serum IGF-1 levels are low, and cortisol secretion may be increased.

This results in oestrogen deficiency. Not all studies have reported bone loss, and it may be that prolactin has some beneficial effects on calcium homoeostasis, such as an increase in calcium absorption.

In the UK, over 250 000 patients take continuous oral glucocorticoids, yet no more than 14% receive any therapy to prevent bone loss, a serious complication of glucocorticoid treatment. Bone loss is rapid, particularly in the first year, and fracture risk may double (13). The mechanism of the bone loss is mainly a suppression of osteoblast activity. This differs from oestrogen deficiency, in which the mechanism is mainly increased activation frequency. A treatment algorithm has been presented for adults receiving glucocorticoid doses for 6 months or more (14). General measures, e.g. alternative glucocorticoids and routes of administration, and therapeutic interventions such as bisphosphonates, are recommended. Glucocorticoid-induced osteoporosis is discussed in greater detail in Chapter 4.11.

Phenobarbitone and phenytoin are known to affect vitamin D metabolism and result in osteomalacia. More commonly, they may cause secondary hyperparathyroidism and osteoporosis.

Thyroxine doses sufficient to suppress thyroid-stimulating hormone, and hydrocortisone doses that result in 24-h urinary free cortisol above the reference range, have adverse effects on bone turnover and bone density (see Chapter 4.8).

Heparin stimulates bone resorption by a direct effect on osteoclasts. Its long-term use (e.g. in pregnancy) results in bone loss at the spine and hip of 8–10% over 6 months. Warfarin may interfere with the γ-carboxylation of bone proteins, and its use is associated with an increased risk of fracture.

This is associated with an increase in bone turnover and a decrease in bone mass, particularly at sites rich in cortical bone. It is likely that there is an increase in fracture rates. These changes are reversible with surgical removal of the tumour (see Chapter 4.3).

This topic is discussed in Chapter 4.8.

Cushing’s disease may present with vertebral fracture. The bone loss in the first few years after pituitary surgery is between 10 and 20% at the spine.

This is associated with decreased bone mass, resulting from excess substitution therapy and deficiency of adrenal androgens (precursors for oestrogen synthesis in men and postmenopausal women).

This may present with vertebral fracture. It is usually identified with serum protein electrophoresis, and urinary Bence Jones testing, but occasionally the myeloma may be nonsecretory and can usually be diagnosed by bone marrow examination.

This may cause decreased or increased bone density. It can be identified by urticaria pigmentosa, and mast cells are identified in the bone biopsy (see Chapter 6.17).

This has been associated with low bone density and increased risk of fractures. The mechanism is unclear, as the absorption of calcium from food is normal despite the absence of gastric acid.

The immobility may be an important cause, as may be the local (and circulating) cytokines, which promote bone resorption. The corticosteroid therapy for rheumatoid arthritis may also contribute.

Diseases such as coeliac disease may present with osteoporosis. Other inflammatory bowel diseases, such as Crohn’s disease, may require treatment with corticosteroids. Patients who have had peptic ulcer surgery have low bone density and increased risk of fracture. This may also be due to their habits—such patients are usually thin, and commonly smoke and may take excess alcohol.

Chronic obstructive liver diseases, such as primary biliary cirrhosis, are associated with osteoporosis. Bilirubin has been associated with osteoblast suppression in vitro. Liver transplantation results in further bone loss and about one-third of patients suffer fractures (15). This bone loss is likely to be related to the immunosuppression (corticosteroids and ciclosporine).

Osteoporosis does not cause pain or deformity in the absence of fractures. Its importance lies in the fact that it greatly increases the risk of fracture, notably forearm (Colles’) fracture, hip fracture, and vertebral fracture. The commonest presentation in clinical practice is vertebral fracture and so this will be described in more detail.

The back pain of vertebral fracture has some characteristic features. The pain often comes on within a day of some strain on the back, such as lifting a suitcase or a grandchild, a jolt on a bus or working in the garden. The pain soon becomes very severe and the patient may need to stay in bed for several days. The pain is usually localized to the back and it is uncommon for pain to radiate into the legs, and symptoms of cord compression such as bladder dysfunction are rare. The pain is present throughout the day and night. The pain gradually eases and goes by 4 to 6 months. If pain persists longer, or if there is a second peak of pain during the first 6 months, this usually indicates a second vertebral fracture. This is not an uncommon occurrence. Patients commonly do not complain of back pain. Indeed, it has been estimated that at least half of vertebral fractures are asymptomatic. These asymptomatic fractures appear to be particularly common in patients taking corticosteroids. Episodes of back pain may have been forgotten. The patient commonly recalls a painful episode when confronted with the appearance of a fracture on the spinal radiograph. This incontrovertible evidence prompts the recall of a painful event occurring many decades previously, often in relation to heavy manual work in a man or after pregnancy in a woman.

Loss of height is an effect of ageing, resulting from the change of posture caused by degenerative changes in the intervertebral discs. Patients do not report this symptom often and it needs to be sought by asking the patient’s height in early adult life. The patient may have noticed that it is more difficult to reach high shelves. It is unusual to have sudden height loss as the presenting complaint for vertebral fracture.

This may have been noticed by a relative or the patient may report being ‘round-shouldered’. Clothes may no longer fit. These symptoms are not specific to vertebral fracture and are more commonly caused by disc degeneration. In a young person, kyphosis may be caused by Scheuermann’s disease (see below).

Vertebral fractures in the lumbar region result in decreased abdominal volume. This causes the abdomen to protrude. Patients with osteoporosis are commonly slender, so this appearance is new. They may also result in impingement of the costal margin on the iliac crest. This ‘iliocostal friction syndrome’ causes pain and a grating sensation. This pain is postural, occurring on sitting. Vertebral fractures in the thoracic spine result in reduced lung volume. This may result in respiratory symptoms, such as dyspnoea, or in delayed recovery from chest infections.

Two aspects of the clinical examination are useful in the patient with suspected vertebral fracture. The first relates to the location of the pain. It is often assumed that the deformity on the radiograph and the patient’s back pain are associated. However, a careful palpation of the spinal processes counting down from vertebra prominens (seventh cervical vertebra) often reveals that the site of the pain does not correspond with the level of the deformity on the radiograph. It is helpful to evaluate the size of the gap between the costal margin and the iliac crest. This is normally three finger’s breadths (as measured by the patient’s fingers).

Plain radiographs are required of the thoracic and lumbar spine in the anteroposterior and lateral position. It is a common mistake to take the radiograph only of the painful area. This would miss asymptomatic fractures in other parts of the spine. It is common only to take lateral radiographs. The anteroposterior radiograph is useful to identify the vertebral level of the fracture and to exclude other causes of deformity, such a malignancy (associated with absent pedicles).

Vertebral deformities may be wedge, endplate (‘biconcave’, when both endplates are affected), and compression (also called ‘crush’) (16). Wedge deformities are particularly common in the thoracic spine, because the normal kyphosis in this region results in the main force running anteriorly. Biconcavity deformities are particularly common in the lumbar spine, because the normal lordosis results in the main force running through the middle of the vertebra. There appears to be no association between the type of deformity and the severity of pain or with the level of BMD. The level of the deformities should be recorded to allow comparison at follow-up visits.

The most common deformity to mimic fracture is Scheuermann’s disease. This is a form of epiphysitis that occurs during adolescence (‘juvenile epiphysitis’) and gives the appearance of wedging and elongation of the vertebral bodies. The characteristic feature is the wavy appearance of the superior and inferior borders.

Malignancy may cause vertebral deformity. The isotope bone scan is particularly useful in this situation as it is unusual to have a single bone lesion. Increased uptake in multiple sites in the skeleton is typical of malignancy. This may occur in prostate cancer, which affects the sacrum, lumbar spine, and ribs (via Batson’s venous plexus). Malignancy may cause erosion of the pedicle, a typical appearance not found with osteoporotic vertebral fractures.

Paget’s disease of bone commonly affects the spine (see Chapter 4.9). The bone may appear sclerotic, but it is weak and can fracture. The bone texture has a disorganized appearance and the vertebra may be enlarged.

Osteomalacia may result in vertebral deformities (see Chapter 4.10). Often adjacent vertebrae are affected and the endplates are deformed. This gives rise to a ‘cod-fish’ appearance. There may be other radiological clues, such as the ground-glass appearance of the vertebral body bone and the presence of pseudofractures (Looser’s zones) in the pelvis, long bones, or ribs.

Dual-energy X-ray absorptiometry (DXA) can be used to image the spine as well as to obtain a measurement of bone density (see below). Vertebral fractures may be identified by careful focus on the appearance of the vertebral endplate (16). Fracture is likely if the endplate is deformed and should be confirmed with a radiograph.

This can be a useful diagnostic tool in certain cases. There is increased isotope uptake in a vertebra for at least 6 months after it has fractured and typically has a uniform distribution in the vertebral body. This can be useful if the radiological appearances are borderline and yet the symptoms are characteristic. In patients with a suspicion of malignancy (previous breast cancer and history of weight loss) the scan is helpful in that metastases often affect many bones. The scan is helpful in a patient with corticosteroid-induced osteoporosis with pelvic pain. These patients commonly develop insufficiency fractures and these show up as symmetrical appearance affecting the sacral alae and the pubic rami. Single photon emission computed tomography is a variant of the isotope bone scan and is particularly useful in identifying the cause of back pain. If the facet joints show increased uptake then the patient may benefit from an injection of local anaesthetic into the facet joint.

This approach can be useful in identifying a recent deformity and distinguishing a fracture from a malignant deposit. It is very useful in identifying cord compression. It is an essential test before kyphoplasty or vertebroplasty are considered (see below); only recent fractures clearly benefit from these procedures.

DXA is precise, accurate, involves exposure to only low doses of X-rays, and allows measurement of sites of clinical interest (that is, lumbar spine and proximal femur). In DXA, two energy peaks of X-rays are absorbed to different extents by bone and soft tissue, and the density of bone is calculated, in g/cm², using simultaneous equations. The measurement is compared with two reference ranges—one for young adults (age 30 years) to give T scores and one for age-matched adults to give Z scores. This has become the standard technique for bone density assessment and guidelines have been proposed (Box 4.7.3). The two sites most commonly used in practice are lumbar spine and total hip. Low BMD at the total hip is a strong predictor of hip fracture (17).

Single energy X-ray (or photon) absorptiometry has similar advantages to DXA, and the equipment is less expensive. However, the sites in which bone density can be measured (distal forearm and calcaneum) may not be of clinical interest.

Quantitative CT allows three-dimensional measurements of the bone density of the lumbar spine. This technique also allows measurement of trabecular bone alone (i.e. the type of bone usually lost first in the development of osteoporosis). In the research setting, finite element modelling can be applied to the information provided by this technique to estimate bone strength. However, quantitative CT is more expensive, less precise, and involves a higher radiation dose then DXA.

Quantitative ultrasound measurements are usually made on the calcaneum. The ultrasound signal has a lower frequency (200–600 kHz) than that used in obstetrics (more than 1 MHz). The attenuation of the signal (broad-band ultrasound attenuation) may reflect both the density and the architecture of bone, and the velocity of the signal reflects the density and biomechanical properties (elasticity). Quantitative ultrasonometry is currently used only in research but, if recent studies of its predictive ability in osteoporosis are confirmed, it could become an established technique.

A secondary cause is present in approximately 40% of women and 60% of men with osteoporosis. The most commonly found abnormalities are those of low vitamin D and either high or low urinary calcium (18). Investigations to identify a secondary cause are recommended if the BMD is more than 2 SD below the age-matched mean or if the patient has low-trauma vertebral fractures (Box 4.7.2).

This may be useful in unusual forms of osteoporosis (e.g. idiopathic osteoporosis in young adults). It provides information about the rate of bone turnover and the presence of secondary forms of osteoporosis (e.g. systemic mastocytosis). Patients with high bone turnover usually respond better to antiresorptive drugs.

These reflect the processes of bone resorption and bone formation (Box 4.7.4). Markers that are specific to bone (e.g. osteocalcin and deoxypyridinoline) may be useful for monitoring the effect of drugs used in the treatment of osteoporosis (19). Biochemical markers of bone resorption may be particularly useful because they are maximally suppressed by 3 months’ treatment with oestrogens or bisphosphonates (see below and Chapter 4.9). They could be more useful than bone density for monitoring treatment because changes in bone density may not be detected for 2 years and not all patients have access to bone densitometry.

The treatment of acute back pain due to a recent vertebral fracture includes:

The treatment of chronic back pain due to vertebral fractures is difficult but includes:

In all patients (with or without fractures), it is important to treat diseases that can increase bone loss and contribute to osteoporosis (Box 4.7.1). An important part of the management of patients with osteoporosis, especially those following hip fracture or other frail patients, consists of attention to their general health status, such as ensuring adequate dietary protein intake, and measures to decrease the risk of falls or the degree of trauma that results from falling. These included better lighting, provision of hand rails, removal of obstacles, attention to drugs such as sedatives and antihypertensives that may predispose to falls, or carpeted surfaces rather than hard floors. Regular exercise may be of value in maintaining mobility and improving muscle mass, thus reducing the risk of falling. Heavy weight-bearing and vigorous exercise programmes should be avoided by patients with osteoporosis as they may trigger the occurrence of a new fracture.

Low calcium intake and vitamin D deficiency should be prevented or effectively treated in all patients. As many hip fractures occur in patients over age 80 years and this population is particularly prone to low calcium intake and vitamin D deficiency (see Chapter 4.10), it is particularly important to ensure that these patients receive adequate calcium and vitamin D as part of their management. Ambulatory patients who receive periodic sunlight exposure generally produce sufficient vitamin D through skin photoconversion, but others should receive a supplement containing at least 800 IU of vitamin D daily. Total intake of calcium, including supplements if necessary, should be at least 1000 mg. Despite the necessity of adequate calcium and vitamin D for bone health, it should be appreciated that treatment with calcium and vitamin D alone is insufficient to prevent postmenopausal bone loss or to markedly reduce fracture risk in patients with osteoporosis.

Drugs to increase bone mass inhibit bone resorption or stimulate bone formation. Most drugs approved for use in osteoporosis inhibit bone resorption, but some of these (e.g. hormone replacement therapy (HRT), bisphosphonates) increase BMD by 5–10% over the first 2 years of treatment.

Antiresorptive drugs—bisphosphonates—are considered the treatment of choice (Table 4.7.2). Their strict dosing instructions may reduce compliance in the elderly. In the UK, five agents are currently approved for use in osteoporosis: etidronate, alendronate, risedronate, ibandronate, zoledronic acid, and raloxifene. The most effective alternative treatments are raloxifene and HRT.

Three other agents can be useful in special circumstances.

Formation-stimulating drugs have been licensed for osteoporosis.

Once patients have been identified and treatment initiated, it is important to ensure adequate follow-up to reinforce the importance of compliance to treatment and evaluate response. At a minimum, all treated patients should be seen initially after 3 to 6 months and thereafter at least annually. The importance of adherence to treatment should be stressed.

Monitoring of response to therapy can be achieved with the use of biochemical markers or repeated BMD measurements, and may be of value in assessing compliance and providing feedback to patients. Although not required, treatment response to oral antiresorptive treatments, such as bisphosphonates, can be evaluated after 3 to 6 months by assessing the change in biochemical markers of bone turnover, such as N-terminal or C-terminal cross-links of type I collagen, serum osteocalcin or serum procollagen I N-propeptide (Box 4.7.4). In most patients these markers decrease by more than 30% relative to pretreatment baseline measurements, and/or are reduced to within the premenopausal reference range, providing evidence that the treatment is having its desired effect to decrease bone turnover. Changes in BMD occur over a longer time frame, and it is generally not useful to repeat the BMD measurement before the end of 1 to 2 years of therapy, and every 2 years thereafter (Fig. 4.7.4). Most patients receiving efficacious therapy can be expected to have a measurable increase in BMD at the spine and hip (especially the trochanter subregion) after 2 years of treatment. The increases in BMD are small at the peripheral sites of measurement, such as the heel or forearm, in relation to the precision of these measurements. Therefore, peripheral sites are unreliable for assessing response in individual patients.

Although osteoporosis is generally regarded as a disease of women, up to 30% of hip fractures and 20% of vertebral fractures occur in men (11). The risk factors for osteoporotic fractures in men include low body mass index, smoking, high alcohol consumption, corticosteroid therapy, physical inactivity, diseases that predispose to low bone mass, and conditions increasing the risk of falls. The key drugs and diseases that definitely produce a decrease in BMD and/or an increase in fracture rate in men are long-term corticosteroid use, hypogonadism, alcoholism, and transplantation. Age-related bone loss may be a result of declining renal function, vitamin D deficiency, increased PTH levels, low serum testosterone levels, low calcium intake, and absorption. Osteoporosis can be diagnosed on the basis of radiological assessments of bone mass or clinically when it becomes symptomatic. Various biochemical markers have been related to bone loss in healthy and osteoporotic men. Their use as diagnostic tools, however, needs further investigation. A practical approach would be to consider a bone density more than 2.5 SD below the young normal mean value (T ≤ -2.5) as an indication for therapy (17). The treatment options for men with osteoporosis include agents to influence bone resorption or formation and specific therapy for any underlying pathological condition. Testosterone treatment increases BMD in hypogonadal men and is most effective in those whose epiphyses have not closed completely. Bisphosphonates (such as alendronate and risedronate) are the treatment of choice in idiopathic osteoporosis (22, 23), with teriparatide in more severe cases (24).