Interventions and Management of Complications of Osteoporosis



Fig. 1
Types of hip fractures (Source: Adapted from Wikipedia Public Domain [WPD]. Accessed 15 April 2016)



Greater trochanteric fractures may be caused by direct injury or may occur following forceful activity of the gluteus medius or minimus muscles, as in certain jumping sports. If found in isolation and displacement is less than 1 cm, without risk of further separation, these fractures can be treated nonoperatively with protected weight-bearing for 6–8 weeks [8]. However, greater trochanteric fractures are commonly found in conjunction with intertrochanteric fractures, which occur in the proximal femur but distal to the femoral neck (Fig. 2). In this case operative intervention for the combined injury would be recommended. Options include sliding screw plate devices that allow for increased osseous healing by bridging bony fragments together, while imparting less stress on the device. A second common intervention used for intertrochanteric fractures is the dynamic hip screw. This may be accompanied by cerclage wires in the case of high-velocity falls (motor vehicle accidents or sports injuries) or when combined with a greater trochanteric injury (Fig. 3).

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Fig. 2
Greater trochanter and intertrochanteric fracture in a single patient. This patient experienced a high velocity fall during a sporting activity. The intertrochanteric fracture is nondisplaced and the greater trochanter is minimally displaced. (Source: Courtesy of Thomas Jefferson University Hospital, Philadelphia, PA)


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Fig. 3
Dynamic hip screw with cerclage wires used in intertrochanteric fracture repair (Source: Courtesy of Thomas Jefferson University Hospital, Philadelphia, PA)

Alternatively, intertrochanteric fractures at low velocity are often seen in those with established osteoporosis. Postoperatively, the patient is made partially weight-bearing (10 %) for 4–6 weeks, depending on the degree of stability. When adequate intertrochanteric healing is evident, progressive weight-bearing is permitted [9]. Subtrochanteric fractures constitute a subgroup of intertrochanteric fractures in which the fracture extends beyond the intertrochanteric line. As with intertrochanteric fractures, the majority of patients are managed with open reduction and internal fixation rather than with an endoprosthesis [2].


Femoral Neck Fractures


Occurring proximal to the greater trochanter, femoral neck fractures (Figs. 4 and 5) carry the added risk of avascular necrosis due to the proximity of the arteries supplying the region of fracture. The Garden classification system I–IV, based on the degree of displacement, is the most commonly used method to characterize femoral neck fractures. Garden I fractures are minimally displaced and incomplete; Garden II fractures are non-displaced and complete; Garden III fractures are partially displaced and complete; and Garden IV fractures are completely displaced. Elderly patients with Garden I or II fractures can be treated with screw fixation.

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Fig. 4
Femoral neck fracture, moderately displaced, left hip (Source: WPD. Accessed 5 Nov 2015)


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Fig. 5
Acute, displaced, comminuted and transverse fracture of the left subcapital femoral neck. This fracture was sustained in a fall from several steps in an elderly female with established osteopenia. (Source: Department of Radiology, Thomas Jefferson University)

Patients with displaced fractures require arthroplasty—the surgical reconstruction or replacement of a joint [10]. The advantages of arthroplasty include lower rates of reoperation, earlier recovery, and possible reduction in the risk of avascular necrosis. Disadvantages are an increase in blood loss and risk of deep wound infection [11]. Patients who are nonambulatory or who have significant medical comorbidities may be treated nonoperatively. However, opting to forego surgery when it is recommended carries an extremely high mortality rate. One study found a 56 % mortality at 12 months post fracture for patients who declined surgery for exclusively economic reasons [12].

One of the benefits of hip arthroplasty is earlier weight-bearing on the surgical limb. For patients with osteoporosis who have undergone arthroplasty for hip fracture, only 22.4 % of those were permitted weight-bearing as tolerated as opposed to 77.7 % of those without osteoporosis [13]. Moreover, the Siebens study [13] found that patients with weight-bearing restrictions were less likely to be discharged home. Ariza-Vega et al. found non-weight-bearing status following hip fracture surgery was associated with diminished functional outcomes after one year [14].


Femoral Shaft and Distal Femur Fractures


For femoral shaft and more distal femur fractures (Fig. 6), pin and screw fixations can be difficult in weakened or osteoporotic bone. The fixation is more robust with the use of a locking compression plate which can provide three times the stability of the standard lateral condylar buttress plates and 2.5 times the strength of the condylar plate in axial loading [15]. However, locking compression plates cannot be placed in cases of periprosthetic fractures, which instead require plates using wires for fixation around the femoral shaft. Periprosthetic fractures can also occur in the supracondylar region but primarily in those patients who have undergone total knee arthroplasty rather than hip arthroplasty [16]. One of the major risk factors for supracondylar periprosthetic fractures after knee surgery comes from a loss of bone mineral density of 19–44 % in the first year postoperatively [17].

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Fig. 6
Left distal femur fracture (Source: Adapted from WPD. Accessed 5 Nov 2015)

From a rehabilitation standpoint, every effort should be made to prevent a periprosthetic fracture following primary or revision hip arthroplasty, given the fact that fixation in this type of injury is so challenging. For this reason and to prevent additional second fractures from falls after an initial injury, large sections of this chapter and those of a number of orthopedic textbooks for training are devoted to prevention of second fractures and healing of initial injuries through nutrition, medication, and physical intervention efforts. If a periprosthetic fracture does occur, the additional surgery necessarily predisposes the patient to further delays in weight-bearing and potentially in restricted weight-bearing for more time than had been the case from surgery for their original hip fracture.



Spinal Fractures


The most common type of spinal fracture in patients with osteoporosis is the anterior wedge compression fracture (Figs. 7 and 8) [18, 19]. As discussed in previous sections, these fractures are most frequently nontraumatic or due to minimal trauma that would not otherwise lead to fracture in a non-osteoporotic patient. Because these injuries typically occur in the thoracic or lumbar spine and involve only the anterior spinal column, the majority of compression fractures are stable and can be managed solely with a thoracolumbosacral orthosis (TLSO brace) [19]. However, patients with severe osteoporosis can experience significant and progressive loss of vertebral body height that can result in increased pain, pulmonary compromise, altered sitting posture, and reduced mobility. In the above situations, surgical options should be strongly considered. In cases where anterior wedging becomes more pronounced and involves 50 % or greater vertebral body height loss, disruption of the posterior longitudinal ligament, and related posterior spinal elements can be assumed. These fractures would then be considered unstable and warrant surgical intervention [20].

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Fig. 7
Diagram showing the microscopic fracture lines within the vertebrae, contributing to a developing compression fracture (Source: WPD. Accessed 23 Nov 2015)


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Fig. 8
X-ray of an L4 vertebral body compression fracture (Source: WPD. Accessed 23 Nov 2015)

Measures of mechanical instability are best seen on a computerized tomography (CT) scan and include a widened interspinous and interlaminar distance, greater than 2 mm of translation in an anterior–posterior direction, kyphosis of more than 20°, dislocation, height loss of greater than 50 %, and the presence of articular process fractures [21]. If a patient with osteoporosis is being managed with just a TLSO brace and experiences either continued severe mid to low back pain with therapy or a sudden increase in back pain, additional imaging by either CT or a combination of anterior–posterior radiographs with a lateral radiograph should be performed [20]. Practitioners need to ensure that a fracture has not progressed to the point of involving posterior ligamentous structures or undergone further vertebral collapse. If the posterior vertebral angle calculated on lateral radiographs exceeds 100° angulation, then a more unstable burst fracture is suspected [22]. In many cases, the lateral view and other assessment tools using a combination of plain radiographs are insufficient to ensure stability, thus making CT imperative [21]. For any patient with suspected spinal fracture instability, therapy should be suspended and flat bed rest reinstated until a confirmatory CT of the thoracolumbar spine can be performed. If any change in the sensory examination accompanies increased pain, an MRI is also required to rule out spinal cord compression or edema [20].

Surgical approaches vary according to the fracture site, the extent of collapsed vertebra, and the degree of osteoporosis, but all practitioners attempt to avoid ending a fusion at the level of greatest mobility such as the thoracolumbar junction. Instead the construct usually extends beyond this junction by one or two levels to avoid termination at the apex of kyphosis [18]. For osteoporotic compression fractures at the thoracolumbar level, the posterior surgical approach provides a relatively safe and direct means of reconstructing damage to posterior spinal elements. Short-segment fusion with two-rod distraction constructs provides correction of kyphotic posture, but this type of surgery carries a high failure rate unless multiple segments both above and below the fracture site are also fused [23]. The additional segments fused will almost certainly compromise spinal mobility postoperatively and create additional challenges in rehabilitation, particularly for activities such as sit-to-stand transfers and reaching. Alternatively, additional placement of an anterior interbody device may decrease risk of posterior construct failure and simultaneously reduce the need for such an extensive posterior fusion [18]. The drawback of a combined anterior and posterior approach is more pain, an additional surgery, and greater risk to a patient with cardiopulmonary disease undergoing anesthesia.

For patients who cannot undergo surgery and who have intractable pain despite opiates, bracing, and rehabilitation strategies, a new hope exists in the form of percutaneous fracture stabilization with polymethyl methacrylate (PMMA). Vertebroplasty involves direct injection of PMMA into a collapsed vertebral body but does not restore vertebral height reduction. In contrast, kyphoplasty uses a balloon tamp to create a void in the bone and expand the vertebra, thereby correcting height loss [24, 25]. While these procedures offer significant pain relief [24, 26], both techniques carry the risk of cement extravasation, although this complication is less frequent with kyphoplasty due to the use of viscous form of PMMA [24, 25].

Another concern with procedures involving PMMA is weakening of adjacent spinal segments. There are inherent risks of incorporating a hard material in close proximity to fragile osteoporotic bone at neighboring vertebral segments. In vertebroplasty patients, long-term follow-up demonstrates a small but significant rise in adjacent segment fracture, relative to segments without PMMA [27]. In one investigation examining kyphoplasty outcomes, a decreased rate of adjacent segment fracture was observed [25]. Kyphoplasty may actually decrease risk of adjacent segment fracture if percutaneous augmentation reestablishes the natural alignment of the spine and eliminates unequal weight-bearing between adjacent vertebrae [24].



Pharmacologic Management: Currently Available Agents


A number of agents exist to treat osteoporosis but due to possible side effects, they should be carefully considered depending on the clinical comorbidities of each patient (Table 1). In addition, the efficacy of the various agents differs based on duration and populations studied within a given clinical trial (Table 2). To assist the clinician with initiating osteoporosis medications based on risk and benefits to an individual patient, the NOF has created guidelines for initiating pharmaceutical agents in postmenopausal women. The qualifying group should have one of the criteria listed in Table 3.


Table 1
Adverse effects of medications for osteoporosis treatment








































Drug

Adverse reactions

Contraindications

Alendronate

Nausea, abdominal pain, musculoskeletal pain, acid regurgitation, flatulence, dyspepsia, constipation, diarrhea

Delayed esophageal emptying, hypocalcemia, inability to be upright for >30 minutes, increased aspiration risk

Ibandronate

Influenza, nasopharyngitis, abdominal pain, dyspepsia, constipation, arthralgia, back pain, extremity pain, myalgia, headache, diarrhea, UTI

Hypocalcemia, delayed esophageal emptying, inability to be upright for >60 minutes

Zoledronic acid

Pain, chills, dizziness, N/V, osteoarthritis, fatigue, dyspnea, headache, HTN, influenza-like illness, myalgia, arthralgia, pyrexia

Hypocalcemia, CrCl <35 mL/min, acute renal impairment

Denosumab

Back pain, anemia, vertigo, upper abdominal pain, peripheral edema, cystitis, URTI, pneumonia, hypercholesterolemia, extremity pain, musculoskeletal pain, bone pain, sciatica, arthralgia, nasopharyngitis

Hypocalcemia, pregnancy

Raloxifene

DVT, PE, hot flashes, leg cramps, infection, flu, headache, N/V, diarrhea, peripheral edema, arthralgia, vaginal bleeding, pharyngitis, sinusitis, cough

VTE history, pregnancy, nursing, women who may become pregnant

Calcitonin

Rhinitis, nasal symptoms, back pain, anthralgia, epistaxis, headache

No absolute contraindications

Teriparatide

Nausea, dizziness, headache, leg cramps, acute dyspnea, allergic reactions, edema, hypercalcemia, injection-site reactions, urticaria, muscle spasm

Hypercalcemia, hyperparathyroidism, CrCl <30 mL/min



Table 2
Effect of osteoporosis medications on bone mineral density






























































Drug

Increase in BMD

Population studied

Study cited

Alendronate

Lumbar spine: 4.8 %

487 postmenopausal women with low bone density received either alendronate 70 mg once weekly and daily placebo identical to raloxifene or raloxifene 60 mg daily and weekly placebo identical to alendronate for 12 months

Sambrook, J Intern Med 2004 [41]

Total hip: 2.3 %

Ibandronate

Lumbar spine: 4.27 %

158 postmenopausal osteoporotic women either received 2 mg IV ibandronate once every three months or 70 mg oral alendronate once per week

Li M, J Bone Miner Metab 2010 [43]

Femoral neck: 3.48 %

Zoledronic acid

Lumbar spine: 6.71 %

3,889 patients (mean age, 73 years) received a single 15-min infusion of zoledronic acid (5 mg) and 3,876 received placebos

Black D, NEJM 2007 [39]

Total hip: 6.02 %

Femoral neck: 5.06 %

Denosumab

Lumbar spine: 5.7 %

228 ambulatory men between the ages of 30 and 85 years with low BMD

Orwoll, J Clin Endocrinol Metab . 2012 Sep [46]

Total hip: 2.4 %

Femoral neck: 2.1 %

Raloxifene

Lumbar spine: 2.2 %

487 postmenopausal women with low bone density received either alendronate 70 mg once weekly and daily placebo identical to raloxifene or raloxifene 60 mg daily and weekly placebo identical to alendronate for 12 months

Sambrook, J Intern Med 2004 [41]

Total hip: 0.8 %

Teriparatide

Lumbar spine: 6.4 %

578 postmenopausal women and older men received a once weekly injection of 56.5 μg of teriparatide over the course of 72 weeks

Sonea, Teruki et al. Bone 2014 [42]

Total hip: 3.0 %

Femoral neck: 2.3 %



Table 3
NOF guidelines for treatment initiation in postmenopausal women [31]





















Previous vertebral hip fracture

T-score below -2 by hip DXA

T-score below -1.5 by hip DXA and 1 or more of the risk factors

Personal history of fracture as an adult

History of fragility fracture in first-degree relative

Low body weight (less than 127 lbs)

Current smoking

Oral corticosteroids (more than three months)


Source: National Osteoporosis Foundation [31]

Bisphosphonates, denosumab, selective estrogen receptor modulators (SERMs), calcitonin, and parathyroid hormone (PTH) constitute the approved pharmacologic agents for prevention and treatment of osteoporosis in women. With the exception of PTH, they all act to inhibit the activity of osteoclasts, effectively reducing bone resorption; for a transient period, formation outpaces resorption. PTH, commercially sold as teriparatide, acts as an anabolic agent to directly stimulate bone formation.

Three bisphosphonates—alendronate (Fosamax), risedronate (Actonel), and zoledronic acid (Reclast)—have been found to improve bone mineral density (BMD), reduce the risk of hip and other nonvertebral fractures, and prevent vertebral fractures. Both alendronate and risedronate are recommended if osteoporosis is caused by overuse of steroid medications, but risedronate also prevents steroid-induced osteoporosis [28]. Because both medications reduce the occurrence of vertebral and nonvertebral fractures by about 50 %, they are currently termed “agents of choice.” Comparative studies of the anti-fracture efficacy of the two drugs have not been conducted and are unlikely to be carried out, given the need to obtain statistical data from more than 500,000 subjects in order to detect even a 10 % difference between alendronate and risedronate [29]. Although both medications have been shown to reduce fracture risk, outcomes are compromised by noncompliance with daily or weekly oral medications [30].

Another bisphosphonate, ibandronate, reduces the incidence of vertebral fractures by approximately 50 % over three years. Whereas these drugs can be taken orally, zoledronic acid (ZA) is administered intravenously which may help to increase adherence to therapy.

Several bisphosphonates can be used for primary and corticosteroid-induced osteoporosis. The long half-life of these medications allows for intermittent dosing on a weekly, monthly, semiannually, and, in the case of ZA, yearly basis [31, 32]. Associated dyspepsia, nausea, fever, or transient bone or muscle pain may occur, depending on the route of administration.

If a patient is affected by hip more than spine osteoporosis, certain bisphosphonates are preferable to others. The Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Recurrent Fracture Trial (HORIZON-RFT) found no difference in nonunion rates between zoledronic acid and placebo when ZA was administered within two weeks, 2–4 weeks, 4–6 weeks, or six weeks after hip fracture repair [33]. An annual infusion of ZA following hip fracture does not result in the additional morbidity and cost of delayed healing. Similar findings have also been found with risedronate [34]. Bone mineral density is improved in osteoporotic postmenopausal women who take alendronate, risedronate, and ZA which have reduced the risk of hip and other nonvertebral fractures [31, 32, 35, 36]; another bisphosphonate, ibandronate, has been shown to be more effective at the spine than the hip [35].

Zoledronic acid is the most potent of the bisphosphonates and has demonstrated significantly better reduction in bone turnover markers relative to alendronate [37]. Patient satisfaction questionnaires found that despite flu-like symptoms associated with ZA for the first three days after infusion, patients preferred this once annual treatment to weekly alendronate doses [38]. In an early large-scale investigation using 5 mg of once yearly intravenous ZA, Black et al. [39] found a 77 % reduction in clinical vertebral fractures after three years, as well as a 41 % decrease in hip fractures. Although risedronate and alendronate have been shown to reduce fracture risk, outcomes are compromised by noncompliance with daily or weekly oral medications [39].

One of the newest treatments for osteoporosis is denosumab (Prolia), a monoclonal antibody that is given subcutaneously to neutralize the receptor activator of nuclear factor-kB ligand (RANKL), linked to bone resorption. Because osteoclasts require RANKL to support their formation and ultimate survival, an antibody added to their existence results in reduction of bone turnover markers. Compliance is also favorable with this agent, given its twice annual administration in a doctor’s office. Unlike zoledronic acid, denosumab is not cleared renally and therefore can be safely administered to those with renal insufficiency [40] (see also Table 2).

Estrogen prevents or delays bone loss in postmenopausal women; however it is associated with an increased risk of breast cancer and is no longer FDA approved for treatment unless other agents cannot be used. Selective estrogen receptor modulators (SERMs) have dual actions as estrogen agonists and antagonists [44] and provide the same benefits as estrogen without its adverse effects. The only SERM thus far sanctioned by the FDA for osteoporotic women is raloxifene which decreases the risk of spine fractures but, as yet, has not been shown to affect hip fracture risk and may not be as effective in preventing bone loss as bisphosphonates [45]. Tamoxifen, a SERM used to treat breast cancer, has been shown to preserve BMD in postmenopausal women [46] and older men [47] but has yet to receive federal approval.

Calcitonin, secreted by thyroid parafollicular cells, acts to suppress osteoclastic activity that leads to small increases in bone mass and reduction in vertebral, but not hip or distal extremity, fracture risk. Approved for women who are at least five years postmenopausal, it is administered intranasally, with potential adverse effects of congestion or epistaxis. Given its limited effect, calcitonin is not considered a first-line treatment.

Parathyroid hormone (teraparatide/Forteo), approved by the FDA as a daily injection in men and women over 28 days, has been demonstrated to increase BMD as well as reduce the likelihood of vertebral and nonvertebral fractures in women. Unlike other treatments, it is an anabolic agent that stimulates bone formation. Reported side effects include hypercalciuria, causing acute gout, leg cramps, or dizziness with orthostatic hypotension [48, 49]. Early studies suggested that concomitant use of bisphosphonates and parathyroid hormone (PTH) would diminish the anabolic effect of PTH. However, the timing of initiation of the respective agents, as well as the population studied, clouded the interpretation of early findings [50].

In contrast, later reports demonstrated that there are gains in combining antiresorptive agents with PTH but primarily for the hip rather than the spine, with two notable exceptions. Zoledronic acid plus subcutaneous daily teriparatide, a form of PTH, resulted in BMD gains in the lumbar spine of 7.5 % after three years. Gains in BMD for patients receiving ZA alone were 7.0 % over three years versus 4.4 % for those receiving teriparatide alone [51]. Although ZA is the only bisphosphonate that thus far produces favorable outcomes in combination with PTH, denosumab combined with PTH has also demonstrated positive gains in spine BMD [50].

Only four of these medications—alendronate, risedronate, zoledronic acid, and teriparatide—have been approved for men (see chapter on male osteoporosis). Head-to-head trials of bisphosphonates have produced insufficient evidence to prove or disprove any single agent’s superiority in preventing fractures; similarly head-to-head trials of bisphosphonates compared to teriparatide or raloxifene have produced insufficient evidence to prove or disprove relative superiority [52].

Although improvement in BMD is an important factor when considering osteoporosis medications, fracture prevention is the ultimate goal. The currently available osteoporosis medications and their effects on fracture prevention are compared in Table 4.


Table 4
Comparison of medication effects on vertebral, nonvertebral, and hip fractures










































































Generic name

Brand name

Reduced risk of vertebral fractures

Reduced risk of nonvertebral fracturesa

Reduced risk of hip fracture

Bisphosphonates

Alendronate

Fosamax

Y

Y

Y

Risedronate

Actonel, actonel with calcium, atelvia

Y

Y

Y

Ibandronate

Boniva

Y

Unknown

Limited to date

Zoledronic acid

Reclast

Y

Y

Y

Biologicals

Denosumab

Prolia

Y

Y

Y

Hormone therapy

Estrogen

Premarin

N

N

N

SERMs

Raloxifene

Evista

Y

N

N

PTH

Teriparatide

Forteo

Y

Y

Potentiallyb


Source: Adapted from: Agency for Healthcare Research and Quality, US Department of Health and Human Services, Reducing the risk of bone fracture: a review of the research for adults with low bone density. 2012. ​effectivehealthc​are.​ahrq.​gov/​index.​efm/​search-for-guides-reviews-andreports/​prod

aNonvertebral fractures affect bones of the appendicular skeleton apart from the hip. Includes distal femur, tibia, humerus, radius

bWeekly injections of 56.5 μg teriparatide may have the potential to reduce the risk of hip fracture. Studies that are designed to determine the effect of teriparatide to reduce the incidence of hip fracture are unavailable and are not likely to be conducted. The human bone biopsy information obtained from the iliac crest may not be representative of the effects of teriparatide at the hip


Pharmacologic Agents on the Rise



Strontium Ranelate


Antiresorptive and anabolic agents remain the two primary drugs of choice for prevention and treatment of osteoporosis. Although antiresorptive agents reduce the rate of bone remodeling, they do not increase BMD. Restoration of BMD and bone formation is not achieved through antiresorptives alone but rather requires the use of anabolic drugs [53]. Strontium ranelate (SR) is a relatively new, orally active drug that has shown positive results in reducing the risk of vertebral fractures in osteoporotic, postmenopausal women [54]. SR has a significant advantage because it decreases bone resorption, and its mechanisms are similar to those of PTH in that it stimulates bone formation and increases BMD.


Vertebral Fractures


In the early 2000s, four randomized placebo-controlled clinical trials emerged that paved the way for introducing SR into osteoporosis treatment and prevention [53, 5557]. In 2002, Meunier et al. were the first to demonstrate SR efficacy on vertebral osteoporosis in a controlled clinical trial [53]. The study population included 353 postmenopausal women with diagnoses of osteoporosis as well as a past medical history positive for a vertebral fracture. The double-blind study compared placebo to three groups receiving SR in doses of 0.5, 1, and 2 g daily for two years. Results effectively demonstrated a dose-dependent increase in BMD in these groups versus a decrease in the placebo-controlled group. Although the primary efficacy measure was lumbar BMD, results also demonstrated a 44 % decreased incidence of fracture in the group receiving 2 g per day SR, compared to the placebo group. Similarly, Meunier et al.’s 2004 study supported findings that over a period of three years, fewer patients treated with SR, as opposed to those given the placebo, experienced new vertebral fractures [54].


Nonvertebral Fractures


Reginster et al. [55] showed that 1 g per day SR for 24 months significantly increased BMD in lumbar spine, femoral neck, and total hip in 160 early postmenopausal women, with no known prior history of osteoporosis. Any dose less than 1 g per day showed no significant effect on BMD. In another clinical trial of 5,091 postmenopausal females given 2 g per day SR for five years, a 19 % relative risk (RR) reduction of major osteoporotic nonvertebral fractures was observed in patients with average risk [56]. In a population identified as high risk, a 36 % RR reduction of hip fracture was exhibited in those receiving 2 g per day SR.

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Aug 17, 2017 | Posted by in PHYSICAL MEDICINE & REHABILITATION | Comments Off on Interventions and Management of Complications of Osteoporosis
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