Osteoporosis In Males


Article Author:
Manuel Bello


Article Editor:
Vishnu Garla


Editors In Chief:
Dustin Constant
Donald Kushner


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes


Updated:
2/11/2019 7:10:14 PM

Introduction

Osteoporosis is a disease which is characterized by decreased bone strength and increased risk of fractures. Classically, this disease has been postmenopausal women however it is increasingly recognized a significant health burden in men as well.  Men also experience higher mortality and morbidity from osteoporotic fractures as compared to women. Also, lack of studies in men, lack of reimbursement for DEXA scans in men, and lack of consensus among organizations are barriers to diagnosis and treatment of osteoporosis in men.[1]

Etiology

About 50% of men have an identifiable cause of osteoporosis, i.e., secondary osteoporosis. When after extensive evaluation no cause is found, it is referred to as age-related osteoporosis in men over 70 years and as idiopathic osteoporosis in men below 70 years. The common secondary causes of osteoporosis in men are as below.

  1. Hypogonadism
  2. Glucocorticoid-induced osteoporosis
  3. Excessive alcohol consumption
  4. Malabsorption
  5. Renal insufficiency
  6. Hyperparathyroidism
  7. Hyperthyroidism
  8. Rheumatoid arthritis[2]

Epidemiology

Although the prevalence of osteoporosis in women is higher than in men, about 30-40% of osteoporotic fractures in men.[3] Fracture incidence in men has a bimodal peak at 15-45 years and then at 75 years of age. The first peak is secondary to traumatic fractures while the second peak is due to osteoporotic fractures.  Also, men have hip fractures about a decade later than women this is especially important in aging populations. The lifetime risk of a 50-year man for osteoporotic fracture is 13-25%.[4] Caucasian women have a hip fracture incidence 3-4 fold higher than Caucasian men, while Asian men and women have almost the same incidence of hip fracture. Although men have a lesser incidence of osteoporotic fractures than women, mortality rates after hip fracture are 2-3 fold higher as compared to women.[1]

Pathophysiology

There are various reasons for the decreased fracture risk in men as compared to women. Bone mass accrual starts from childhood, and it increases exponentially during puberty. Although men tend to have this acceleration later as compared to women they can achieve higher peak bone mass due to larger bones and greater periosteal expansion. These larger bones lead to greater biomechanical strength and decreased fracture risk. While the areal bone density is greater in men, volumetric bone density as measured on computed tomography (CT) is the same as that of women.[5]

Trabecular bone loss starts in the three decades in men and women. However, this accelerates in women after menopause. In men, bone loss is more gradual. On the other hand, men undergoing androgen deprivation therapy (ADT) do experience a sharp decrease in bone mass and an increase in the risk of fracture. Trabecular bone loss in women involves the decline in the number of trabeculae, whereas in men the trabecula undergo thinning, but their number remains constant. This difference in the mechanism of bone loss could also potentially contribute to the decreased fracture risk in men.[5][6]

History and Physical

Osteoporosis in men is an underdiagnosed condition. A detailed history of previous fractures needs to be elicited. The presence of a fracture even a traumatic one increases the odds of developing osteoporosis later on in life. A history of height loss (>6 cm) may indicate osteoporosis. The physical exam should include an assessment of gait and balance. The prevalence of secondary osteoporosis in men is as high as 50%. A focussed history and physical assessing for the presence of secondary causes of osteoporosis is detailed below.

1. Endocrine causes:

a. Cushing syndrome: Easy bruising, weight gain, irregular periods, hirsutism, decreased libido, hoarseness, new onset diabetes mellitus and hypertension, facial plethora, moon facies, abdominal obesity, broad red striae, gynecomastia, supraclavicular fat pad elevation, buffalo hump, and thin extremities.

b. Hypogonadism: Decreased libido, gynecomastia, loss of muscle mass, a decrease in shaving frequency, fatigue, irregular periods, hot flashes.

c. Hyperparathyroidism: Hypercalcemia, polyuria, polydipsia, nephrolithiasis.

d. Hyperthyroidism: Increase in appetite, weight loss, tremors, palpitations, insomnia, amenorrhea, goiter, and heat intolerance.

2. Systemic causes:

a. Malabsorption: Weight loss, diarrhea, abdominal pain, signs of vitamin deficiencies.

b. Chronic liver disease: Loss of appetite, jaundice, pruritis, ascites, palmar erythema, spider nevi.

c. Multiple myeloma: Loss of appetite, weight loss, lytic bone lesions, hypercalcemia.

d. Anorexia nervosa: Weight loss, body image distortion, amenorrhea, and low BMI.

3. Genetic causes:

a. Osteogenesis imperfecta: History of recurrent fractures, blue sclera, family history of osteogenesis imperfecta, yellow teeth, triangular face, and frontal bossing.

b. Hypophosphatasia: History of frequent fractures, tooth loss, bowed legs.

4. Medications:

a.  Glucocorticoids, Cyclosporin-A, Tacrolimus, Heparin, Aromatase inhibitors, Anticonvulsants, and Long term heparin.

 Osteoporosis is also associated with various disorders like rheumatoid arthritis, diabetes mellitus, chronic obstructive pulmonary disease (COPD), cancer and organ transplantation.[7]

Evaluation

Laboratory assessment needs to specific to each patient based on history and physical exam. 

  • Serum chemistries - Renal insufficiency, Hypercalcemia secondary to hyperparathyroidism
  • 25 (OH) vitamin D - Vitamin D deficiency
  • 24-hour urinary calcium - Idiopathic hypercalciuria
  • 1 mg dexamethasone suppression test - Cushing syndrome
  • Serum and urine electrophoresis - Multiple myeloma
  • Thyroid function tests - Hyperthyroidism
  • Testosterone levels - Hypogonadism
  • Serum prolactin - Prolactinoma
  • Celiac antibodies - Celiac disease

Dual-energy x-ray Absorptiometry (DEXA) scan is the gold standard imaging modality for the diagnosing osteoporosis. A T-score of <-2.5 is diagnostic of osteoporosis and a  T-score of -1 to -2.49 is consistent with osteopenia.

Fracture risk assessment tool (FRAX) is used to determine the risk of fracture in the next ten years. A FRAX score of >3% for hip fracture or 20% for other major osteoporotic fracture in a patient with osteopenia is an indication for anti-osteoporosis treatment.[7]

Treatment / Management

Screening:

ISCD, NOF, Endocrine Society recommend routine screening of men over 70 years with a DEXA scan. In men aged 50-69 years with a history of fractures or other risk factors, screening is also recommended. However, UPSTF has not recommended the screening of osteoporosis in men due to lack of evidence.

Lifestyle interventions:

Inadequate physical activity is associated with a higher risk of falls. 30-40 mins of weight-bearing exercise 3-4 times/week have been shown to reduce the risk of falls. It is recommended to quit alcohol and smoking as they have been shown to decrease the risk of fracture.

Calcium and Vitamin D supplementation:

The Institute of Medicine (IOM) recommends 1000 mg of calcium per day in men aged 51-70 years and 1200 mg of calcium in men aged over 70 years. Vitamin D levels need to be checked in high-risk cases like malabsorption, liver disease, history of falls and osteomalacia. A vitamin D of greater than 30 ng/ml is adequate for optimal none health. Adequate levels may be achieved by administering vitamin D 2000 IU/day, or 50,000 IU/week for eight weeks or 300,000 IU every three months.

Testosterone:

Testosterone therapy can increase bone mineral density, and muscular strength which decreases falls, Younger men with organic causes of hypogonadism and with mild to moderate risk of fracture can use testosterone therapy instead of specific osteoporosis treatment however those with a high risk of fracture need both testosterone and anti-osteoporotic therapy.

Anti-osteoporosis therapy:

Anti-osteoporosis therapy is indicated in men with fragility fractures, with a T-score of less than -2.5, with a T-score of -1 to -2.5 and a FRAX of greater than 3% at the hip and 20% of any fracture, and those on long term steroids (>7.5 mg of prednisone). 

Bisphosphonates: Oral bisphosphonates (alendronate and risedronate)have been shown to increase bone mineral density and decrease fracture risk. Intravenous zoledronic acid has been shown to reduce the risk of vertebral fracture by 67% in men as compared to placebo. Side effects of bisphosphonates include esophagitis, osteonecrosis of the jaw and atypical femoral fractures. An acute phase reaction with fever and myalgias has been associated with zoledronic infusions.

Denosumab: Denosumab is a RANK-L monoclonal antibody, it inhibits the RANK-L pathway which mediates bone resorption. In a phase 3 trial, it increased vertebral and femoral bone density by 5.7% and 2.4% respectively.[1][8]

Pearls and Other Issues

  • Osteoporosis in men is a growing problem in the USA. Men develop osteoporosis a decade later than women and also experience higher mortality and morbidity.
  • Men have decreased fracture risk as they have larger bones, and do not experience an abrupt cessation of sex steroids. Trabecular bone loss is also secondary to trabecular thinning and not the loss of trabeculae.
  • About 50% of men tend to have an identifiable cause of osteoporosis. Therefore a careful evaluation for secondary causes of osteoporosis needs to be done.
  • Treatment involves lifestyle changes, treatment of secondary causes and anti-osteoporosis therapy.

 

Enhancing Healthcare Team Outcomes

The diagnosis and management of osteoporosis are best achieved with a multidisciplinary team that consists of an endocrinologist, primary care provider, nurse practitioner, dietitian, and radiologist. The key is to perform a screening test to identify males at risk and a history of fractures. The primary care provider and nurse practitioner are in the prime position to educate the patients on lifestyle interventions that include discontinuing tobacco, alcohol, eating healthy, and participating in physical activity. For males treated with bisphosphonates, close monitoring is vital as these drugs also have potent adverse effects. Data show that while these agents can strengthen bone, the risk of fractures does not significantly decrease.[9][10] (Level V)

 

 

 

 

 


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Osteoporosis In Males - Questions

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During the screening of a 72-year-old male, it is discovered that he has moderate bone thinning and is at risk for bone fracture. What is the current first-line treatment for such patients?



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When can men be diagnosed with idiopathic osteoporosis?



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A 40-year-old male patient presents with back pain for 2 weeks. Lumbar x-rays revealed multiple compression fractures. There has been no history of trauma. Past medical history is significant for a recent history of diabetes mellitus. On examination, facial plethora, abdominal obesity, and wide red striae were noted. What is the next best step in the assessment of this patient?



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A 75-year-old male patient presents to the clinic for follow up. He recently had a recent DEXA scan with a T-score of -3.0 at the femoral neck. He also has a history of fatigue and loss of muscle mass. Laboratory assessment is as follows: basic metabolic panel-normal, vitamin D- 22nE/ml, 24-hour urinary calcium excretion: 180 mg/24 hrs, total testosterone: 6 ng/dl, prolactin: 20 ng/ml. Which of the following is the best treatment option in this patient?



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Osteoporosis In Males - References

References

Gennari L,Bilezikian JP, New and developing pharmacotherapy for osteoporosis in men. Expert opinion on pharmacotherapy. 2018 Feb;     [PubMed]
Seeman E, Osteoporosis in men: epidemiology, pathophysiology, and treatment possibilities. The American journal of medicine. 1993 Nov 30;     [PubMed]
Johnell O,Kanis JA, An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2006 Dec;     [PubMed]
Burge R,Dawson-Hughes B,Solomon DH,Wong JB,King A,Tosteson A, Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2007 Mar;     [PubMed]
Duan Y,Beck TJ,Wang XF,Seeman E, Structural and biomechanical basis of sexual dimorphism in femoral neck fragility has its origins in growth and aging. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2003 Oct;     [PubMed]
Wang XF,Duan Y,Beck TJ,Seeman E, Varying contributions of growth and ageing to racial and sex differences in femoral neck structure and strength in old age. Bone. 2005 Jun;     [PubMed]
Lewiecki EM, Osteoporosis: Clinical Evaluation 2000;     [PubMed]
Watts NB,Adler RA,Bilezikian JP,Drake MT,Eastell R,Orwoll ES,Finkelstein JS, Osteoporosis in men: an Endocrine Society clinical practice guideline. The Journal of clinical endocrinology and metabolism. 2012 Jun;     [PubMed]
Yang Y,Qiu S,Tang X,Li XR,Deng LH,Wei Q,Fu P, Efficacy and Safety of Different Bisphosphonates for Bone Loss Prevention in Kidney Transplant Recipients: A Network Meta-Analysis of Randomized Controlled Trials. Chinese medical journal. 2018 Apr 5     [PubMed]
    [PubMed]

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