Ashish K Jose

Serum homocysteine levels and the risk of Osteoporosis

Ravichandran S¹, Ashish K Jose ², Krishnagopal R ³, Surendher Kumar R⁴

¹Dr. Ravichandran S, ²Dr Ashish Kumar Jose, ³Dr. Krishnagopal R, ⁴Dr. Surendher Kumar R. All are affiliated with Department of Orthopaedics, Mahatma Gandhi Medical College & Research Institute, Pondicherry, India.

Address for Correspondence: Dr. Ashish Kumar Jose, Email:joseashish@yahoo.co.in

Abstract

Introduction: Osteoporosis is a major health problem which has devastating health consequences through its association with osteoporotic fractures. Prevention of osteoporosis by identifying the risk factors is a major challenge in the field of medicine. Elevated homocysteine level in blood can be a potential risk factor for the development of osteoporosis. We aim to study if a person with high circulating level of homocysteine has a decreased Bone Mineral Density (BMD), thus establishing an association between homocysteine and the risk of developing osteoporosis. Method: Patients between the age group of 40-70 years attending BMD camps between July 2015 and December 2015 were included in the study. All of them underwent BMD test and blood samples were sent to the laboratory for estimation of serum homocysteine levels. The results were collected and analyzed to see if there was any association between serum homocysteine levels and osteoporosis. Results: Out of the 58 males and 20 females with normal BMD, none had elevated serum homocysteine. 21 out of the 58 males and 47 out of the 82 females with osteopenia had elevated serum homocysteine. Of the 27 males with osteoporosis, 25 had elevated serum homocysteine while among the 125 females with osteoporosis, all 125 had elevated serum homocysteine levels. Conclusion: From our study we concluded that people with high circulating level of homocysteine had a decreased Bone Mineral Density (BMD), thus establishing an association between homocysteine and the risk of developing osteoporosis.

Key Words: Homocysteine, Osteoporosis, BMD, Serum homocysteine levels

Manuscript received: 3rd March 2016, Reviewed: 14th March 2016
Author Corrected: 23rd March 2016, Accepted for Publication: 4th April 2016

Introduction

Osteoporosis is a major health problem characterized by low bone mineral density (BMD) and increased risk of fractures [1]. Osteoporotic fractures are associated with increased morbidity and mortality & cause substantial financial loss to the patients and their families [2,3,4]. Elevated levels of homocysteine in the blood is associated with an early onset of osteoporosis [5,6].An elevated plasma homocysteine level (>15 mmol/l) is prevalent in 30 – 50 % population above 60 years [5,6]. High homocysteine levels have been associated with an increasedrisk of fractures, although the factors that contribute tothis fracture risk are not fully elucidated. Homocysteine is anintermediary amino acid formed by the conversion of methionineto cysteine. Elevated serum homocysteine levels show clinical manifestations involving the eyes, blood vessels, nervoussystem and skeleton including the development of earlyosteoporotic fractures.Vitamin B12 and folic acid play an important role in homocysteine metabolism [7]. They are co-factors in homocysteine metabolism and their intake can help in reducing serum homocysteine levels [8,9,10]. We aim to study if a person with high circulating level of homocysteine has a decreased Bone Mineral Density (BMD), thus establishing an association between homocysteine and the risk of developing osteoporosis.

Methods

The study population included patients between the age group of 40-70 years attending BMD camps organized by the department of Orthopaedics, Mahatma Gandhi Medical College, Pondicherry, between July 2015 and December 2015. Both male and female patients were included in the study. Patients with previous fractures and those on long term steroids were excluded from the study. All of them underwent BMD test by DEXA scan. Blood samples were collected and sent to the laboratory for estimation of serum homocysteine levels.

The BMD values were interpreted as follows:
Normal : 1 to -1
Osteopenia : -1 to -2.5
Osteoporosis : Below -2.5
The normal serum homocysteinelevel : 15 mmol/L

The results of both BMD scan and serum homocysteine levels were collected and analyzed to see if there was any association between serum homocysteine levels and osteoporosis.

Results

During the study period of 6 months, 370 patients attending the BMD camps fell into our inclusion criteria and were included in our study. Of them 143 were males and 227 were females (Table 1).

Table 1: Age Distribution

Age group (years)	Males	Females
40-50	43	61
51-60	73	112
61-70	27	54
Total	143	227

The average BMD in the age group of 40-50 years was -0.72 in males and -1.6 in females. In the 51-60 years age group it was -1.47 in males and -2.53 in females. The average in 61-70 years age group was -2.61 in males and -3.4 in females (Table 2).

Table 2: Average BMD levels

Age group (years)	Males	Females
40-50	-0.72	-1.6
51-60	-1.47	-2.53
61-70	-2.61	-3.4

In the patients with normal BMD the average serum homocysteine level was 5.4 mmol/L in males and 7.2 mmol/L in females. Osteopenic individuals showed an average serum homocysteine level of 14.1 mmol/L in males and 16.2 mmol/L in females. Those with osteoporosis showed average serum homocysteine level of 38.7 mmol/L in males and 46.1 mmol/L in females (Table 3).

Table 3: Average serum homocysteine levels

BMD	Males (mmol/L)	Females (mmol/L)
Normal	5.4	7.2
Osteopenia	14.1	16.2
Osteoporosis	38.7	46.1

Of the 43 males in the 40-50 years age group, 7 were osteopenic and the rest had normal BMD, while among the 61 females in the same age group, 35 were osteopenic and 6 were osteoporotic. Among the 73 males in the 51-60 years age group, 46 were osteopenic and 5 were osteoporotic, while among the 112 females in the same age group, 47 were osteopenic and 65 were osteoporotic. Out of the 27 males in the 61-70 years age group, 5 were osteopenic and 22 were osteoporotic, while among the 54 females in the same age group all 54 were found to have osteoporosis (Table 4).

Table 4: Age and sex wise distribution of BMD results

	40- 50 years		51-60 years		61-70 years
BMD	Male	Female	Male	Female	Male	Female
Normal	36	20	22	Nil	Nil	Nil
Osteopenic	7	35	46	47	5	Nil
Osteoporotic	Nil	6	5	65	22	54
Total	43	61	73	112	27	54

Out of the 58 males and 20 females with normal BMD, none had elevated serum homocysteine. 21 out of the 58 males and 47 out of the 82 females with osteopenia had elevated serum homocysteine. Of the 27 males with osteoporosis, 25 had elevated serum homocysteine while among the 125 females with osteoporosis, all 125 had elevated serum homocysteine levels (Table 5).

Table 5: Relation between BMD and elevated serum homocysteine

	Male		Female
BMD	BMD	S. Homocysteine Elevated	BMD	S. Homocysteine elevated
Normal	58	Nil	20	Nil
Osteopenic	58	21	82	47
Osteoporotic	27	25	125	125
Total	143	46	227	172

Discussion

Osteoporosis is a metabolic bone disease. It is the leading cause of fractures with advancing age leading to pain, hospitalization and increased financial burden to the patient and his family. Even though it is considered as a normal ageing process, osteoporosis can be prevented and treated if detected early. Elevated serum homocysteine level or hyperhomocysteinemia is considered to be one of the possible modifiable risk factors of osteoporosis.

Homocysteine is a sulfur containing amino acid that is formed by methionine metabolism. It is metabolized in the body by remethylation or trans-sulfuration pathway (Fig.1).

Fig 1 :Homocysteine metabolism pathway

The normal serum homocysteine level is considered to be below 15mmol/L. A raised serum homocysteine level can be due to multiple factors – lifestyle, diet, hormonal [11]. Hyperhomocysteinemia is considered to be a potential risk factor for the development of osteoporosis [12,13]. Vitamin B12 acts as a co-factor in the remethylation of homocysteine to methylene [14]. Hence vitamin B12 deficiency can lead to elevated serum homocysteine levels.

A study done by van Meurs et al concluded that elevated serum homocysteine levels lead to a 2 fold increase in the incidence of fractures [15]. Another study by Bucciarelli et al showed inverse association of serum homocysteine and BMD in post- menopausal women [16]. Tyagi et al concluded that hyperhomocysteinemiacan lead to reduced blood flow in the bones compromising bone quality [17]. A study done by Enneman et al in 2014 showed that elevated serum homocysteine was associated with a decreased BMD [18].

Similarly in our study we found an inverse correlation between serumhomocysteine levels and BMD. Out of the 58 males and 20 females with normal BMD, none had elevated serum homocysteine. 36 % males (21 out of 58) and 57% females (47 out of 82) with osteopenia had elevated serum homocysteine levels. However when it came to people with osteoporosis on BMD, 93 % males (25 out of 27) and 100% of females (125 out of 125) had elevated serum homocysteine levels. The average serum homocysteinelevelsin osteoporotic individuals were 38.7 mmol/L in males and 46.1 mmol/L in females. Hence we see a definite relation between elevated serum homocysteine level and osteoporosis.

Conclusion

Osteoporosis is a major health problem which has devastating health consequences through its association with osteoporotic fractures. Prevention of osteoporosis by identifying the risk factors is a major challenge in the field of medicine. Bone metabolism is affected by homocysteine. Elevated homocysteine level in blood is a potential risk factor for the development of osteoporosis. From our study we concluded that people with high circulating level of homocysteine had a decreased Bone Mineral Density (BMD), thus establishing an association between homocysteine and the risk of developing osteoporosis. Vitamin B12 and folic acid play an important role in homocysteine metabolism [7].Supplementation with vitamin B12 and folic acid has been shown to normalize plasma homocysteine levels. This could reverse the problem of impaired bone health and osteoporosis and help in preventing osteoporotic fractures.

Funding: Nil, Conflict of interest: None initiated.
Permission from IRB: Yes

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How to cite this article?

Ravichandran S, Ashish K Jose, Krishnagopal R, Surendher Kumar R, Serum homocysteine levels and the risk of Osteoporosis: Int J Med Res Rev 2016;4(4):557-561. doi: 10.17511/ijmrr.2016.i04.14.