O s t e o p o ro s i s i n O l d e r

Adults
Catherine Bree Johnston, MD, MPH*, Meenakshi Dagar, MD

KEYWORDS
 Osteoporosis  Postmenopausal osteoporosis  Older adults

KEY POINTS
 Osteoporosis-related fractures of the hip, vertebra, and pelvis are a common cause of
morbidity and mortality in older adults.
 All healthy adults should be counseled about measures to prevent osteoporosis, including
adequate calcium and vitamin D intake, participating in weight-bearing exercise, and
avoiding tobacco and excess alcohol consumption.
 Women should be screened for osteoporosis beginning at age 65. Screening for osteopo-
rosis in men should be considered when risk factors are present. Appropriate screening
intervals are controversial.
 Women and men with osteoporosis should be offered pharmacologic therapy. Choice of
therapy should be based on safety, cost, convenience, and other patient-related factors.
Bisphosphonates are often first-line therapy based on efficacy, safety, and cost.

DEFINITION

Osteoporosis is a disease characterized by low bone mass and disruption of bone ar-
chitecture, resulting in compromised bone strength and increased fracture risk. Oste-
oporosis is also considered a silent disease, as there are commonly no symptoms until
the first fracture occurs.
The World Health Organization defines osteoporosis using bone mineral density
(BMD) and T score. T score represents a standard deviation (SD) that calculates
how much a result varies from the average or mean bone mineral density of a healthy
young adult. A T score of 0 means that BMD is equal to the norm for a healthy young
adult. The more SDs below 0, indicated as negative numbers, the lower the BMD and
higher the risk of fracture. Osteoporosis is defined as a T score of < 2.5. Osteopenia,
or low bone density, is defined as a T score of 1.0 to 2.5 (Table 1).

Division of Geriatrics, General Internal Medicine, and Palliative Medicine, Department of

Medicine, University of Arizona College of Medicine, Banner University Medical Center, 1501
North Campbell Avenue, Suite 7401, Tucson, AZ 85724-5801, USA
* Corresponding author.
E-mail address: [email protected]

Med Clin N Am 104 (2020) 873–884

https://doi.org/10.1016/j.mcna.2020.06.004 medical.theclinics.com
0025-7125/20/ª 2020 Elsevier Inc. All rights reserved.
874 Johnston & Dagar

Table 1
T score criteria for normal range, osteopenic range, and osteoporotic range

Normal Bone density is within 1 SD (T score 11 to 1) of the young adult mean

Osteopenia Bone density is 1–2.5 SDs below the young adult mean (T score 1 to 2.5)
Osteoporosis Bone density is 2.5 SDs or more below the young adult mean (T score < 2.5)

PREVALENCE

Worldwide variation in the incidence and prevalence of osteoporosis is difficult to

determine because of problems with underdiagnosis. The best way to compare oste-
oporosis in different population groups is by looking at the fracture rates in older indi-
viduals. As osteoporosis is not a life-threatening condition, data from developing
countries are scarce. Worldwide, osteoporosis causes more than 8.9 million fractures
annually, resulting in an osteoporotic fracture every 3 seconds.1 Osteoporosis is esti-
mated to affect 200 million women worldwide:
Approximately one-tenth of women aged 60
One-fifth of women aged 70
Two-fifths of women aged 80
Two-thirds of women aged 902
One in 3 women over age 50 years will experience osteoporotic fractures, as will 1 in
5 men aged over 50 years.3
Data from the 2005 to 2010 National Health and Nutrition Examination Survey
(NHANES) suggested that in the United States, 16.2% of adults aged 65 and over
had osteoporosis at the lumbar spine or femur neck. The age-adjusted prevalence
of osteoporosis at either skeletal site was higher among women (24.8%) than men
(5.6%). The unadjusted prevalence was higher among adults aged 80 and over
(25.7%) than for adults aged 65 to 79 (12.8%). The age-adjusted prevalence of oste-
oporosis was highest among Mexican American adults (24.9%), followed by non-
Hispanic white adults (15.7%), and was lowest among non-Hispanic black adults
(10.3%). Asian ethnicity was not included in the data.4
NHANES also found that 48.3% of adults aged 65 and over had osteopenia or low
bone density at the lumbar spine or femur neck. Women had a higher age-adjusted
prevalence of low bone mass at either skeletal site (52.3%) than men (44.0%). Adults
aged 80 years and over had a higher unadjusted prevalence of low bone mass (52.7%)
than adults aged 65 to 79 years (46.7%). Non-Hispanic black adults had the lowest
age-adjusted prevalence of low bone mass (36.7%), while non-Hispanic white and
Mexican American adults had similar age-adjusted prevalence of low bone mass
(49.4% and 47.3%, respectively).4

RISK FACTORS

Risk factor for osteoporosis can be characterized as potentially modifiable and non-
modifiable and are listed in Table 2. Some common risk factors are discussed in
more detail.
Diet
A healthy diet in childhood is an important contributor to peak bone mass, and main-
taining a healthy diet can help reduce bone loss in later life. Adequate dietary protein,
calcium, vitamin D, fruits, and vegetables have a positive influence on bone health,
 Osteoporosis in Older Adults 875

Table 2
Osteoporosis risk factors

Gender Women are at higher risk than men

Age Risk increases with age
Ethnicity African Americans are at lower risk than Asians, Hispanics, and
non-Hispanic whites
Family history Osteoporosis in first-degree relatives increases risk
Body size Small, thin-framed people are more at risk
Sex hormones Amenorrhea
Menopause and premature ovarian failure
Hypogonadisim in men
Thyrotoxicosis
Panhypopituitarism
Hyperprolactinemia
Body weight disorders Body mass index <17
Anorexia nervosa
Malabsorptive bariatric surgery
Calcium and vitamin D A lifetime diet low in calcium and vitamin D is a risk factor for
osteoporosis
Medications Anticonvulsants
Glucocorticoids (>5 mg/d of prednisone or equivalent
for 5>3 mo), GnRH antagonist/agonist, SSRIs,
thiazolidinediones, aromatase inhibitors
Lifestyle An inactive lifestyle or extended bed rest/immobilization
Cigarette smoking Increased risk with consumption
Alcohol Increased risk with excessive intake
Comorbid illness Hypercalciuria
Osteogenesis imperfecta
Homocystinuria
Hemochromatosis
Glycogen storage disease
Cystic fibrosis
Celiac disease
Cushing syndrome
Inflammatory bowel disease
Diabetes mellitus

while a high caloric diet has been associated with lower bone mass and higher rates of
fracture.5

Alcohol Use and Smoking

A meta-analysis based on 18 prospective cohort studies revealed a nonlinear associ-
ation between alcohol consumption and the risk of hip fracture. Light alcohol con-
sumption (0.01–12.5 g/d) appears to be associated with a slightly reduced risk of
fracture, whereas heavy alcohol consumption (>50 g/d) is associated with an
increased hip fracture risk.6
Cigarette smoking is a risk factor for osteoporosis. Smoking causes reduction in
circulating levels of 1,25-dihydroxyvitamin D and parathyroid hormone (PTH).
Smokers have small but significant reductions in bone mineral density when
compared with nonsmokers.7
876 Johnston & Dagar

Glucocorticoids
Glucocorticoid (GC)-induced osteoporosis is the most common secondary cause of
osteoporosis. It is estimated that 3% of the population 50 years of age and older
has used GCs, and this percentage increases to 5.2% in 80 years of age and older.8
Thirty percent of patients with long-term GC use (>6 months) develop osteoporosis.9
Bone loss is more pronounced in the trabecular bone, predominantly in the spine and
ribs.10 The increase in fracture risk is dose dependent, and the effect is at least
partially reversible once the GC is discontinued.

Diabetes Mellitus
Type 1 diabetes mellitus is associated with low BMD, and the risk increases with the
duration of disease. Data from Health Survey done in Norway showed a significant in-
crease in hip fracture rates among females with type 1 diabetes (relative risk 6.9, con-
fidence interval 2.2–21.6) compared with nondiabetic female patients. The mechanism
of bone loss in unknown.11
Type 2 diabetes mellitus was earlier believed to cause increased BMD. These re-
ports were primarily based on the concept of BMD and not from prospective
controlled trials. Patients with generally larger body size and relatively high bone
mass have higher fracture rates. Bone quality changes are related to microvascular
events common in diabetes. A large prospective study of older women obtained
from the Study of Osteoporotic Fractures, confirmed that female patients with type
2 diabetes experience higher fracture rates in regions of the hip, humerus, and foot
compared with nondiabetic female patients.12

OSTEOPOROSIS COMPLICATIONS

Bone fractures are the most serious complication of osteoporosis. Fractures can
occur at any bone site, but are most common in the hip and vertebrae. Fractures
may lead to chronic pain, disability, depression, nursing home stay, reduced quality
of life, and increased mortality. Pain from fracture is often the first presenting symptom
of osteoporosis. Because of weakened architecture of vertebral bone, minor fractures
over time can cause compression fracture. It can also lead to a condition called
kyphosis, sometimes called dowager’s hump. Vertebral fractures are the most preva-
lent osteoporotic fractures and are paradoxically the most underdiagnosed. Vertebral
fractures are the predictors of future fracture risk; the probability is fivefold for subse-
quent vertebral fractures and twofold to threefold for fractures at other sites.13
Hip fractures occur usually after a fall. Hip fractures are associated with 15% to 20%
increased mortality rate within 1 year, with a higher mortality rate in men than in
women, followed by a 2.5-fold increased risk of future fractures. Approximately
20% to 50% hip fracture patients require long-term nursing home care and suffer
from decreased quality of life, social isolation, depression, and loss of self-esteem.13
Multiple vertebral thoracic fractures may result in restrictive lung disease and wors-
ened pulmonary function in women with pre-existing lung disease. Lumbar fractures
may decrease the volumes between the ribs to the pelvis, alter abdominal anatomy,
crowd internal organs (particularly the gastrointestinal [GI] system, causing GI com-
plaints such as premature satiety, reduced appetite, abdominal pain, constipation,
and distention); further, back pain (acute and chronic), prolonged disability, poor
self-image, social isolation, depression, and positional restriction are other problems
created by compression fractures in addition to increased mortality.14
 Osteoporosis in Older Adults 877

NONPHARMACOLOGIC MEASURES FOR PREVENTION AND TREATMENT OF

OSTEOPOROSIS

Once peak bone mass has been attained (ie, in middle and late middle age), the goal of
prevention is to reduce the rate of bone loss. Prevention strategies include nutrition,
exercise, and lifestyle factors.
Nutrition strategies include adequate calcium and vitamin D intake. The recommen-
ded calcium intake for postmenopausal women and men over age 70 is 1200 mg/d15
Most adults do not require calcium supplementation. The US Preventive Services Task
Force concluded that evidence was insufficient to recommend calcium supplementa-
tion for primary prevention (USPSTF).16 The recommended intake of vitamin D is 600
to 800 IU daily, which can be difficult to achieve by diet alone.17,18 Many older adults,
particularly those with low dietary intake or those who are at risk of vitamin D defi-
ciency (eg, homebound patients) benefit from supplementation. Screening for vitamin
D deficiency is not recommended routinely in asymptomatic adults, but may be
considered in patients at high risk for vitamin D deficiency. Although the ideal serum
level of vitamin D is controversial, some experts recommend supplementation with
a target serum level of 25-OH vitamin D above 20 to 30 ng/mL.18
Providers should recommend exercise to patients for multiple health benefits.
Weight-bearing and/or resistance activity on most or all days of the week can help
maintain muscle mass and BMD. Structured exercise and balance programs (eg, tai
chi) can help reduce falls.18,19
All patients should be advised to eliminate or minimize the potentially reversible risk
factors that have been discussed previously.
All older adults, but particularly older adults with osteoporosis, should be counseled
in fall prevention strategies, including exercise, particularly strength and balance
training, reduction or elimination of sedative-hypnotic medications, and environmental
modifications.15,18,19

FRACTURE RISK ASSESSMENT TOOL

Risk assessment is most commonly conducted using the Fracture Risk Assessment
Tool (FRAX), which is a tool that helps predict a patient’s 10-year risk of hip or other
major osteoporotic fracture. It has been validated for untreated patients aged 40 to
90 years in multiple countries and for multiple ethnicities. It can be accessed at
www.sheffield.ac.uk/FRAX. Limitations of FRAX include that it is limited to only 4 eth-
nicities in the United States (Caucasian, Black, Hispanic, and Asian) and lack of vali-
dation in treated patients.20,21

SCREENING FOR OSTEOPOROSIS

The US Preventive Service Task Force and other societies recommend screening for
osteoporosis in all women aged 65 and older.15,18,19,22 Screening should be conduct-
ed at the hip and spine using dual energy-x-ray absorptiometry (DXA). Some guide-
lines recommend screening younger women with osteoporosis risk factors, but
there is no consensus on how to optimally manage osteoporosis in this age group.
Men should not be routinely screened for osteoporosis; however, they should be eval-
uated with DXA if they have risk factors for osteoporosis (eg, hypogonadism,
androgen deprivation therapy, long-term glucocorticoid therapy, or celiac disease),
loss of height, or fragility fractures.15,18,19
Screening intervals are controversial. One study suggested a screen interval of 10 to
15 years for older women with baseline T scores of > 1.5, 5 years for those with
878 Johnston & Dagar

moderate osteopenia (T score < 1.5 and >>-2.0) and 1 year for those with advanced
osteopenia (T score < 2.0 and > 2.5), but this is not a consensus recommendation.23
When to stop screening is also controversial.15 It is reasonable to discontinue
screening if treatment would not be considered based on comorbidities or patient
preferences, or if life expectancy is so short (ie, less than 1–2 years) that the patient
would be unlikely to benefit from treatment.

DIAGNOSIS

The diagnosis of osteoporosis can be made in the presence of a fragility fracture,

particularly at the spine, hip, wrist, humerus, rib, or pelvis without measurement of
BMD can also be made in the presence of a T score of no more than 2.5 SDs at
any site based on measurement by DXA. Several professional organizations also sup-
port making the diagnosis when the 10- year probability of a major osteoporotic frac-
ture is greater than 20% or the 10 year probability of hip fracture is greater than
3%.15,18,19
Most experts recommend laboratory evaluation with a complete blood count, a
chemistry panel that includes calcium, phosphorous, and alkaline phosphatase, and
a 25-hydoxyvitamin D level. Further evaluation is indicated when there is suspicion
for hyperthyroidism, celiac disease, multiple myeloma, hypogonadism, or
hyperparathyroidism.15,18,19

TREATMENT

All men and women who meet the criteria for the diagnosis of osteoporosis should be
counseled about nonpharmacologic preventive measures including exercise, diet,
smoking cessation, and reduction of fall risk.15,18,19

Pharmacologic Treatment
Both women and men with osteoporosis should be offered pharmacologic treatment,
although the evidence for benefit is stronger in women than in men. Table 3 summa-
rizes commonly used agents, dosing guidelines, adverse effects and precautions.
Some guidelines recommend treating women with osteopenia with a 10-year proba-
bility of hip fracture of greater than or equal to 3% or a 10-year probability of any major
osteoporosis related fracture of greater than or equal to 20%, while other guidelines
suggest used a shared decision making framework in these situations based on pa-
tient preferences, risk profile, benefits, harms, and costs of medications. Reduction
in fracture risk with pharmacologic therapy has only been demonstrated with diag-
nosis based on DXA in the osteoporotic range or with previous fragility fracture, not
when a risk assessment tool such as FRAX is used.15,18,19,24
Evidence is insufficient to determine the comparative effectiveness of different phar-
macologic agents for the treatment of osteoporosis; therefore, choice of therapy
should be based on safety, cost, convenience, and other patient-related factors
(see Table 1).24
The antiresorptive agents include bisphosphonates, denosumab, selective estro-
gen receptor modulators (SERMs), and estrogen/progestin therapy. Anabolic agents
include the parathyroid hormone/parathyroid related protein analogs teriparatide
and abaloparatide and the monoclonal antibody romosozumab.
Bisphosphonates
The bisphosphonates (risedronate, alendronate, ibandronate, and zoledronic acid) are
effective therapies for established osteoporosis. To ensure optimal absorption, the
 Osteoporosis in Older Adults 879

Table 3
Most commonly used osteoporosis drugs

Efficacy of
Fracture Adverse Effects, Cost,
Reduction Usual Dosing Other Considerations
Hip (H)
Vertebral (V)
Nonvertebral (NV)
Bisphosphonates As a class, osteonecrosis
of jaw (rare)
As a class, atypical
fracture (rare,
increased with
longer duration of
use)
Alendronate H, V, NV 70 mg orally weekly GI symptoms
Generic is <$100/mo
Risedronate H, V, NV 35 mg orally weekly GI symptoms
5 mg orally daily $100–$200/mo
Zoledronic Acid H, V, NV 5 mg intravenously Arthralgias, myalgias,
yearly headache,
hypocalcemia, atrial
fibrillation
Generic <$100/mo
Ibandronate V 150 mg orally monthly Usually avoided
because of lack of
evidence of evidence
for hip and
nonvertebral
fractures
GI symptoms, cramps,
myalgias
$100–$200/mo
Other Antiresorptive
Agents
Denosumab H, V, NV 60 mg subcutaneously Mild upper GI
every 6 months symptoms, rash,
infections
Increased risk of
vertebral fractures
after d/c
Jaw osteonecrosis of
jaw (rare)
Atypical fracture (rare,
increased with
longer duration of
use)
$200–$300/mo

(continued on next page)

880 Johnston & Dagar

Table 3
(continued )
Efficacy of
Fracture Adverse Effects, Cost,
Reduction Usual Dosing Other Considerations
Raloxifine V 60 mg orally daily Thromboembolic
events, hot flashes
<$100/mo
Anabolic agents
Teriparatide V, NV 20 mg subcutaneously Mild GI symptoms,
daily hypercalcemia, renal
events
>$1000/mo
Romosozumab V, NV 210 subcutaneously Potential for serious CV
monthly events
Injection site reactions
$1000–$2000/mo

oral forms should be taken in the morning with at least 8 ounces of water, in an upright
position, with no other ingestions for at least 40 minutes. Even with these measures,
there is a risk of esophagitis and upper GI symptoms. These agents are not recom-
mend in patients with esophageal disorders or a creatinine clearance blow 35 mL/
min 25-OH vitamin D, and calcium deficiency should be corrected prior to initiation
of these agents.15,18,19,24
The intravenous (IV) bisphosphonates (zoledronic acid and abandronate) can be uti-
lized for patients who cannot tolerate oral bisphosphonates (ie, inability to sit up for
40 minutes). IV bisphosphonates are sometimes associated with hypocalcemia and
influenza-like symptoms.15,18,19,24
For patients taking bisphosphonates, most guidelines suggest reassessment of
risk, including bone mineral densitometry, after 5 years of oral bisphosphonate ther-
apy or 3 years of IV bisphosphonate therapy. Patients at continued high risk at 3 or
5 years because of low hip T score, a high fracture risk score, or history of fracture
on therapy, should be considered for continued bisphosphonate therapy. The
maximum duration of therapy is 10 years for oral bisphosphonates and 6 years for
IV bisphosphonates. It should be noted that most data are based on osteoporosis
in women, and data on optimal management in men are more limited.15,18,19,24
The risk of atypical subtrochanteric fracture increases with duration of therapy. In 1
study, the rate of atypical fracture was 1.78 per 100,000 in women taking the drug for
less than 2 years (number needed to harm >50,000), increasing to 100 per 100,000 in
women taking the drug for 8 years or more (number needed to harm 1000).25 Both
bisphosphonates and denosumab are associated with the rare complication of osteo-
necrosis of the jaw, which is most commonly seen in patients with severe dental
disease.15,18,19,24

Denosumab
Denosunab is as a human monoclonal antibody that acts on the key bone resorption
mediator RANKL, thus inhibiting osteoclast formation and survival. It has been shown
to increase BMD and reduce the incidence of fracture in postmenopausal women. The
risk of vertebral fracture appears to increase following discontinuation, making it less
attractive as a first-line agent. Denosumab should be considered when there is a
contraindication to bisphosphonate therapy (eg, reduced creatinine clearance). Like
 Osteoporosis in Older Adults 881

bisphosphonates, denosumab is associated with the rare complication of osteonec-

rosis of the jaw. It also is associated with an increased risk of infection, mild upper
GI symptoms, and rash. Because of the increased risk of fractures following discon-
tinuation of therapy, continuing therapy or administration of another agent following
discontinuation should be considered.15,18,19,24,26

Selective estrogen receptor modulators

Raloxifene inhibits bone resorption and reduced the risk of vertebral fracture, but there
is no evidence that it reduces the risk of hip fracture, and for that reason, it is consid-
ered a second-line agent. It has potential benefits in reducing the risk of breast cancer,
but that it offset by an increased risk of thromboembolic events and hot flashes. It
should be considered when the risk of breast cancer is high and there are contraindi-
cations to other agents. It is unclear how long SERMs can be safely administered;
many clinicians discontinue therapy at 8 years because of lack of safety data beyond
that time frame.15,18,19,24
Tamoxifen is used for the prevention and treatment of breast cancer but should not
be used as a primary agent for osteoporosis. However, women receiving tamoxifen
probably receive benefits in BMD.15,18,19,24

Sex hormones
Sex hormone replacement may help prevent bone loss in men and women who have
other indications for their use (eg, hypogonadism in men, hot flashes in women), but
should not be used for established osteoporosis due to lack of efficacy.15,18,19,24

Parathyroid hormone/parathyroid hormone-related protein analogs

Teriparatide and abaloparatide are anabolic agents that stimulate bone formation and
activate bone remodeling. They are not considered first-line agents for most patients
because of cost. They should be considered in women or men with severe osteopo-
rosis (T score of < or 5 3.5 or T score < or 5 2.5 with a fragility fracture), in patients
who are unable to tolerate other therapies, or in patients who fail other therapies.
Adverse effects include mild upper GI symptoms, hypercalcemia, and depression.
They should not be used longer than 24 months because of a potential risk of osteo-
sarcoma (observed in rats). Patients at high risk for fracture following discontinuation
should be treated with an antiresorptive agent.15,18,19,24

Romosozumab
Romosozumab is a monoclonal antisclerostin antibody that has been shown to in-
crease BMD and reduce vertebral and nonvertebral fractures. In has been associated
with an increased risk of serious cardiovascular events.27 It should be considered only
for patients who fail other agents and are at low risk for adverse cardiovascular out-
comes. Therapy is limited to 12 monthly doses. Patients at high risk for fracture
following discontinuation should be treated with an antiresorptive agent.27,28

Other agents
Bazedoxifine is a SERM that is used in Europe and Japan for women with osteopo-
rosis. It is also used in combination with estrogen for the prevention of osteoporosis.
It is not used in the United States for treatment of osteoporosis.29 Calcitonin is no
longer used to treat osteoporosis. However, it may have analgesic properties that
can be helpful in the setting of acute osteoporotic vertebral fractures.30

Special populations and considerations

There is evidence that bisphosphonates and teriparatide are effective for older pa-
tients as well as younger patients.24 In general, the evidence is insufficient to draw
882 Johnston & Dagar

strong conclusions about the efficacy of pharmacologic treatment of osteoporosis in

men.24 There is some evidence that alendronate, risedronate, and teriparatide are
effective in patients taking glucocorticoids.31

CLINICAL CARE POINTS

FRAX helps predict a patient’s 10 year risk of hip or other major osteoporotic fracture,
and can help guide treatment decisions. Fall prevention strategies can reduce the risk
of fracture in patients with osteoporosis.
IV bisphosphonate use should be reassessed after 3 years of use; only patients with
significant risk of future fracture should continue. Six years is the maximum duration of
therapy for IV bisphosphonates.
Oral bisphosphonate use should be reassessed after 5 years of use; only patients
with significant risk of future fracture should continue. Ten years is the maximum dura-
tion of therapy for oral bisphosphonates.
The risk of vertebral fracture appears to increase following discontinuation of deno-
sumab. It should either be continued indefinitely or followed by administration of
another agent.
The risk of atypical fractures of the femur increases with duration of use of
bisphosphonates and denosumab. The complication is rare but potentially serious.

SUMMARY

Osteoporosis and its associated complications are common causes of morbidity and
mortality in older adults. All healthy adults should be counselled about measures to
prevent osteoporosis, including adequate calcium and vitamin D intake, participating
in weight-bearing exercise, and avoiding tobacco and excess alcohol consumption.
Women should be screened for osteoporosis beginning at age 65. Screening for
osteoporosis in men should be considered when risk factors are present. Appropriate
screening intervals are controversial.
Women and men with osteoporosis should be offered pharmacologic therapy.
Choice of therapy should be based on safety, cost, convenience, and other patient
related factors. Duration of therapy depends on agent chosen and the patient’s risk
for future fractures.

DISCLOSURE

Neither author has anything to disclose.

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