Diagnosis and Treatment of Osteoporosis

What Orthopaedic Surgeons Need to Know

Elizabeth G. Matzkin, MD; Marlene DeMaio, MD; Julia F. Charles, MD, PhD; Corinna C. Franklin, MD

J Am Acad Orthop Surg. 2019;27(20):e902-e912.

Abstract and Introduction

Abstract

Osteoporosis, often called a silent disease, is a systemic condition of bone as a result of loss of bone mass and deterioration of its microarchitecture. The result is weakened bone, leading to an increased risk of fragility fractures. An estimated 9 million osteoporotic fractures occur every year worldwide. However, the true incidence of osteoporotic fractures is unknown because many are undetected. Astoundingly, this epidemic equates to an osteoporotic fracture every 3 seconds. Orthopaedic surgeons need to not only treat these fractures but also understand the underlying pathogenesis and risk factors to help prevent them. The management of osteoporosis is a critical part of musculoskeletal care. We must be familiar with the tools to assess osteoporosis and the treatments available, including risks and benefits. This review article is intended to deliver a review of the vast literature and provide the orthopaedic surgeon with the essential information necessary to manage the current osteoporosis epidemic.

Introduction

Osteoporosis has been defined by the National Osteoporosis Foundation (NOF) as a "bone disease that occurs when the body loses too much bone, makes too little bone, or both."^[1] The World Health Organization operationally defines osteoporosis as a bone mineral density (BMD) measure by a dual-energy x-ray absorptiometry (DXA) that is "2.5 standard deviations or more below the average value for young healthy women (a T-score of <−2.5 SD).^[2] As bone becomes less dense and weaker, there is an increased susceptibility to fracture. In both men and women, bone mass increases until approximately age 30 years after which it starts to decline. This decline is accelerated in women after menopause secondary to the decrease in estrogen levels resulting in an approximate 2% loss in BMD each year. Women usually have a lower BMD than men to begin with, and coupled with a more rapid loss in BMD, it results in the much higher rates of osteoporosis. According to the International Osteoporosis Foundation, one in three women and one in five men older than 50 years will experience an osteoporosis-related fracture.^[3] Osteopenia is defined as a T score of less than −1.0 and is estimated to effect an even higher percentage of the population.

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Table 1. Factors and Their Effect on Bone Remodeling ⁵
Factor	Effect on Bone
Calcium (Ca)	90% of body calcium is stored in bones; a decrease in serum Ca will result in increase in bone resorption
Vitamin D	Helps increase Ca absorption
PTH	Stimulates the production of IL-6, which increases osteoclast formation and increases bone resorption; can also work to increase bone formation
1,25 dihydroxyvitamin D (calcitriol)	Stimulates the release of calcium in the blood
Calcitonin	Decreases bone resorption by inactivating osteoclasts
TSH	T3 and T4 stimulate osteoblasts
Estrogen	Regulates osteoclasts by inhibiting formation and increasing apoptosis (inhibits bone resorption)
Testosterone	Increases the proliferation and apoptosis of osteoblasts, converted to estrogen

PTH = parathyroid hormone, TSH = thyroid-stimulating hormone

Table 2. Risk Factors for Osteoporosis
Demographic	Female sex
	White race
	Increasing age
Dietary	Low calcium
	Low vitamin D
	Disordered eating/RED-S
Historical	Family history of osteoporosis or fracture
Historical	Personal history of fracture
Hormonal	Low estrogen
	Late menarche
	Early menopause
	Hypogonadism in men
Medication	Glucocorticoids
	Thyroid medication
	Anticonvulsants
Lifestyle	Smoking
Lifestyle	Limited exercise
Secondary	Diabetes
	Hyperparathyroidism
	Hyperthyroidism
	Alcoholism
	Malabsorption
	Multiple myeloma
	Rheumatoid arthritis
	Inflammatory bowel disease

RED-S = relative energy deficiency in sport

Table 3. Evaluation of the Patient With Suspected Osteoporosis ^11–13
Tools with scores associated with osteoporosis	Simple Calculated Osteoporosis Risk Estimation (SCORE, Merck): ≥6
	Osteoporosis Risk Assessment Instrument (ORAI): ≥9
	Osteoporosis Index of Risk (OSIRIS):<1
	Osteoporosis Self-Assessment Tool (OST): <2
	FRAX: computer algorithm
Screening tests	Bone mineral tests:
	Central DXA—measures the hip and lumbar spine
	Peripheral DXA—measures the forearm and calcaneus
	Bone biopsy
	Quantitative ultrasonography
Laboratory tests	Serum calcium, phosphate, creatinine with an estimated glomerular filtration rate, alkaline phosphatase, liver function, 25-hydroxyvitamin D, and glucose complete blood count
	24-hr urine calcium, creatinine, and sodium

DXA = dual-energy x-ray absorptiometry

Table 4. Indications for BMD Testing ^12,13,15,16
Women	Women aged ≥65 yr
	Secondary osteoporosis
	Postmenopausal women with
	Low-energy fractures
	Incidental finding of radiographic fracture (spinal compression fx)
	Glucocorticoid treatment >3 mo
	Peri- or postmenopausal women
	Menopause before age 40 yr
	Family history of osteoporotic fractures
	Risk factors below
Men	Men aged ≥70 yr
Men	Men aged 50–69 yr with risk factors below
Women and Men	Low body weight
	Previous low-energy fracture
	Smoking
	Within at least 6mo of initiation of glucocorticoid treatment (all adults aged ≥40 yr and adults aged <40 yr with high fracture risk)

BMD = bone mineral density

Table 5. Antiresorptive Agents
Drug	Trade Name	Route	Typical Dosing Regimen	Sites With Demonstrated Fracture Risk Reduction	Estimated Cost, 1-mo Supply^a	Contraindications
Diphosphonates
Alendronate	Fosamax Binosto (effervescent tablet)	per os per os	70 mg weekly 70 mg weekly	Vertebral, nonvertebral, and hip	$1.16	CrCl < 35 mL/min Esophageal disorders including Barrett esophagus Roux-en-Y gastric bypass Vitamin D deficiency
Risedronate	Actonel	per os	35 mg weekly	Vertebral, nonvertebral, and hip	$108	CrCl < 30 mL/min Esophageal disorders including Barrett esophagus Roux-en-Y gastric bypass Vitamin D deficiency
Ibandronate	Boniva	per os	150 mg monthly,	Vertebral	$6.80	CrCl < 30 mL/min Esophageal disorders including Barrett esophagus Roux-en-Y gastric bypass Vitamin D deficiency
Ibandronate	Boniva	IV	3 mg every 3 mo	Vertebral	$57	CrCl < 30 mL/min Vitamin D deficiency
Zoledronic acid	Reclast	IV	5 mg yearly	Vertebral, nonvertebral, and hip	$87	CrCl < 35 mL/min Vitamin D deficiency
Other
Denosumab	Prolia	subcutaneous	60 mg every 6 mo	Vertebral, nonvertebral, and hip	$196	Hypocalcemia Vitamin D deficiency Pregnancy
Raloxifene	Evista	per os	60 mg daily	Vertebral	$17	History of Thromboembolism
Calcitonin	Miacalcin Fortical	Intranasal subcutaneous	200 IU daily 100 IU every other day	Vertebral	$258	Hypersensitivity to salmon products Hypocalcemia Vitamin D deficiency

^aBased on the National Drug Acquisition Cost as of January 23, 2019, from https://data.medicaid.gov. Pricing provided is for generics, when available. Cost to consumer varies widely depending on prescription benefits and eligibility for manufacturer rebates, grants, and/or copay assistance.

Table 6. Anabolic Agents
Drug	Trade Name	Route	Typical Dosing Regimen	Demonstrated Fracture Risk Reduction	Estimated Cost, 1-mo Supply^a	Contraindications
Teriparatide	Forteo	SQ	Once daily forup to 24 mo	Vertebral and nonvertebral	$3,179	Hyperparathyroidism Hypercalcemia History of radiation therapy Paget disease of bone Unexplained elevated alkaline phosphatase History of skeletal metastases
Abaloparatide	Tymlos	SQ	Once daily for up to 24 mo	Vertebral, nonvertebral, and hip	$1,771	Hyperparathyroidism Hypercalcemia History of radiation therapy Paget disease of bone Unexplained elevated alkaline phosphatase History of skeletal metastases
Romosozumab (not yet FDA approved)	Evenity	SQ	Monthly for 12 mo	Vertebral, nonvertebral, and hip	Not yet available

SQ = subcutaneous
^aBased on the National Drug Acquisition Cost as of January 23, 2019, from https://data.medicaid.gov. Pricing provided is for generics, when available. Cost to consumer varies widely depending on prescription benefits and eligibility for manufacturer rebates, grants, and/or copay assistance.

Table 7. Resources for Osteoporosis Risk Assessment
Risk Assessment Tool	URL
FRAX	https://www.sheffield.ac.uk/FRAX/
FRAX desktop version	https://www.frax-tool.org
SCORE (Simple Calculate Osteoporosis Risk Estimation)	https://reference.medscape.com/calculator/osteoporosis-risk-score
IOF 1-minute risk test	https://www.iofbonehealth.org/iof-oneminute-osteoporosis-risk-test
Garvan Institute fracture risk calculator	https://www.garvan.org.au/promotions/bone-fracture-risk/calculator
FORE 10-yr fracture risk calculator	https://riskcalculator.fore.org
American bone health calculator	https://americanbonehealth.org/calculator/