Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
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An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
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Aug 2018

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Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
On May 11,2011

Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
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Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."

Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
On April 2011

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.

Dr. Anuradha
On Jan 2020

Important Notice

Original article / research
Year : 2022 | Month : June | Volume : 16 | Issue : 6 | Page : RC01 - RC04 Full Version

Comparing the Effectiveness of Oral versus Intramuscular Vitamin D Supplementation in Adults with Fracture around Hip and Vitamin D Deficiency

Published: June 1, 2022 | DOI:
Sidhant Chhabra, Anand Sharma, Som Pratap Gupta, Ashwani Bilandi, Mohit Meena, Ashwani Kumar Mathur

1. Junior Resident, Department of Orthopaedics, Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan, India. 2. Associate Professor, Department of Orthopaedics, Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan, India. 3. Professor and Head of Department, Department of Orthopaedics, Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan, India. 4. Senior Resident, Department of Orthopaedics, Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan, India. 5. Assistant Professor, Department of Orthopaedics, Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan, India. 6. Professor, Department of Orthopaedics, Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan, India.

Correspondence Address :
Dr. Ashwani Kumar Mathur,
Professor, Department of Orthopaedics, Mahatma Gandhi Medical College and
Hospital, Jaipur, Rajasthan, India.


Introduction: Cholecalciferol plays vital role in bone mineralization. Major circulating and storage form of vitamin D is 25-hydroxycholecalciferol {25(OH)D3} which is formed in the liver after 25-hydroxylation. It is also the form of vitamin D that is measured in blood tests to detect deficiency of vitamin D. There is scarcity of literature to support the best therapy at the lowest effective dose that is practicable, cost efficient, and devoid of probable side effects. Oral medication compliance is a major stumbling block to replenishing vitamin D levels in the body. Vitamin D administered intramuscularly (i.m.) may be able to overcome this limitation.

Aim: To compare the effectiveness of oral versus intramuscular vitamin D in adults with fracture around hip and vitamin D deficiency.

Materials and Methods: This prospective interventional study was conducted in Orthopaedics Ward in Mahatma Gandhi Institute of Medical Sciences, Jaipur, Rajasthan, India, from January 2020 to June 2021. Total 60 male and female, above 18 years, with fractures around the hip and vitamin D levels less 30 ng/mL were included in the study. In group O (n=30) patient received oral vitamin D supplementation of 60000 IU once a week for 6 weeks . In group I (n=30) patient received single dose of 600000 IU vitamin D injection (i.m.). Follow-up of patients was done at baseline, 6 weeks and 12 weeeks for serum values of vitamin D, calcium, alkaline phosphatase and parathyroid hormone levels. Bivariate analytical techniques has been used to measure the improvement of group I with group O.

Results: The mean age in group I was 60.40±16.38 years and in group O was 59.47±15.17 years (p-value=0.82). There were total 31 females, 13 in group I and 18 in group O. No significant difference was observed among the groups in vitamin D level at the baseline, {group I: 13.84 ± 3.54 ng/mL; group O: 16.45 ± 6.3 ng/mL, p-value=0.053}. At 6 weeks, the mean value of the vitamin D significantly increased in both groups (p-value=0.001; group I: 40.94±4.67 ng/mL and group O: 33.64±9.89 ng/mL). At the 12th week, the mean value of the vitamin D was significantly higher in group I (44.52±7.09 ng/mL) compared to group O (24.65±10.92 ng/mL), p-value<0.001. The vitamin D mean was significantly raised with the time in group I and group O at 6 weeks and still remained increased at 12 weeks in group I but not in group O.

Conclusion: The present study concluded that although both administration routes are effective and appear to be safe, intramuscular application is more effective in increasing 25(OH)D levels and sustaining it for a longer period of time as compared to oral dose.


Bone metabolism, Cholecalciferol, Effective dose, Osteoporosis

Vitamin D plays a very significant role in bone metabolism and mineralization. It is a fat soluble vitamin, leads to its effects by acting on vitamin D receptors (1). Lesser mineralization of bones leads to rickets and osteomalacia (2). It has a preventive role in various diseases like in cancer, infection, autoimmune illness, cardiovascular diseases, and diabetes mellitus, among other non skeletal disorders (3).

The high prevalence of hypovitaminosis D among pregnant women and children is a major concern. Weather changes has also reflected changes in vitamin D levels (4). In large cities, air pollution probably also plays a role (5). Urban subjects are found to be more deficient in vitamin D (6). One-fifth of them also have indications of parathyroid hyperactivity, as measured by PTH levels in the blood (7). Their hypovitaminosis D is caused by a lack of sunlight exposure and skin pigmentation (8). There are studies which have shown decreased levels of vitamin D in neonates, healthy school girls, hospital staff, pregnant women in North India (5),(8),(9),(10).

In most of the studies, the criteria used for defining hypovitaminosis (vitamin D Deficiency) is serum 25(OH)D level below 50 nmol/L (9),(10),(11). Various vitamin D deficiency and insufficiency diseases have been highlighted (12). In adults, this can lead to decreased mineralization that is Osteomalacia. Decreased levels also leads to increased incidences of hip fractures muscle weakness thus affecting the mobility and functional ability of the person (13),(14). Prevention of such eventualities is feasible by adequate sunlight exposure, food fortification and supplementation of vitamin D for at risk population as a cost-effective measure in prevention of hip and other geriatric fractures.There is need for optimizing vitamin D levels in cases of osteoporosis patients given antiresorptives (bisphosphonate) and anabolic (teriparatide) drugs (15). Active vitamin D works in tandem with two additional hormones to maintain calcium and phosphate homeostasis and Parathyroid Hormone (PTH) (16).

Physicians in India are currently prescribing a 1500 mg cholecalciferol sachet to be taken once a week for 1 to 8 weeks for overt or occult vitamin D insufficiency (17).

Its short-term and long-term effects on serum 25(OH)D levels in Asian Indians, however, have not been well investigated. There is a scarcity of scientific literature to support the best therapy at the lowest effective dose, that is practicable, cost-efficient and devoid of probable side effects. Persistence is very low with oral vitamin D supplementation (18). Oral medication compliance is a major stumbling block to replenishing vitamin D levels in the body. Vitamin D administered intramuscularly (i.m.) may be able to overcome this limitation. Vitamin D i.m. injections are regularly available in the market in two values (3 lac and 6 lac IU). Parenteral route (intramuscular) of administration of vitamin D has lead to effective increase in vitamin D levels but this cannot be administered without monitoring serum levels (19).

Supplementation, either oral or intramuscular, is a more realistic and easier way to receive enough vitamin D. However, no study comparing intramuscular injection and oral vitamin D dosage in Indian people has been conducted. Hence, present study was conducted to evaluate the efficacy and tolerability of oral cholecalciferol (60,000 IU) versus i.m. cholecalciferol (600,000 IU) in correcting vitamin D deficiency with fracture around hip.

Material and Methods

This prospective interventional study was conducted among patients, admitted to Orthopaedics Ward in Mahatma Gandhi Institute of Medical Sciences, Jaipur, Rajasthan, India, from January 2020 to June 2021. The study was permitted by Institutional Ethics Committee (MGMCH/IEC/JPR/2020/100).

Inclusion criteria: All males and females above 18 years of age, with hip fractures and vitamin D levels less than 30 ng/mL were included in the study (2).

Exclusion criteria: The patients taking Hormone Replacement Therapy (HRT) or anticonvulsants, with chronic debilitating illness {Chronic Obstructive Pulmonary Disease (COPD), cancer, Acquired Immune Deficiency Syndrome (AIDS), Congestive Heart Failure (CHF)}, renal disease (creatinine level >1.5 mg/dL), liver disease (bilirubin >2 mg/dL), malabsorption syndrome and patients with gastrectomy/steroid dependency were excluded from the study.

Sample size calculation: For sample size calculation, power was taken as 80%, from similar previous study by Gupta N et al., where they have used 40 samples, 20 in each arms with power 80% and level of significance 5% (20). In present study, 10 more samples in each group 30 (total n= 60) were taken.

A total 60 patients were divided equally into two groups (30 patients each group). Randomization was done by chit in box method.

• Group O (n=30): Received oral vitamin D supplementation of 60,000 IU once a week for 6 weeks.
• Group I (n=30): Received i.m. vitamin D supplementation with a single dose of 6,00,000 IU vitamin D injection.


A 10 mL of fasting blood samples were collected for measurement of serum vitamin D, serum calcium (albumin-adjusted) and serum Parathyroid Hormone (PTH), Alkaline Phosphatase (ALP) levels.

1. Serum 25(OH)D level was determined by radioimmunoassay method (19).

• Vitamin D deficiency: <10 ng/mL
• Insufficiency: 10- 29 ng/mL
• Optimal: ≥30 ng/mL

3. Serum calcium was measured with the enzymatic method using automated spectrophotometer the reference range for serum calcium is 2.20-2.60 mmol/L (21).

Follow-up was done for oral vitamin D, intramuscular vitamin D, PTH level and calcium at baseline, at 6 weeks and at 12 weeks.

Statistical Analysis

Continuous data were summarized in the form of mean and their standard deviation. Difference in change in means of two groups were analysed using student’s t-test (difference in differential analysis). Intragroup analysis of means at multiple time duration was analysed using Analysis of Variance (ANOVA). Count data were expressed in form of proportions. Difference among proportions were analysed using Chi-square test. The level of significance was kept 95% for all statistical analysis. Statistical Package for Social Sciences (SPSS) software version 14.0 (Inc.,Chicago, IL, USA) was used for all analytics works.


The groups were comparable according to age and sex demographics. Mean age in group I was 60.40±16.38 years and in group O was 59.47±15.17 years (p-value=0.82). There were total 31 females, 13 in group I and 18 in group O (Table/Fig 1). In present study, 52 (86.67%) were found to be vitamin D deficient and 8 (13.33%) were vitamin D insufficient.

At baseline, no significant difference was observed between the groups for vitamin D (p-value=0.053). At 6th week, the mean value of the vitamin D increased in both groups. Mean value was significantly higher in group I (40.94±4.67 ng/mL) as compared to group O (33.64±9.89 ng/mL) (p-value=0.001). At 12th week, the mean value of the vitamin D was significantly higher in Group I (44.52±7.09 ng/mL) as compared to Group O (24.65±10.92 ng/mL) with p-value <0.001 (Table/Fig 2).

Statistically no significant difference was observed in the Calcium level at baseline, 6th week and 12th week during follow-up between the groups as shown in (Table/Fig 3).

(Table/Fig 4) shows the difference in ALP values over time between two groups. Baseline values in the two groups were comparable. At 6th week, the mean value of the ALP decreased from the baseline in both the Group I and Group O. No significant difference was observed between the groups at 6th week (p-value=0.506) and 12th weeks (p-value=0.495).

(Table/Fig 5) depicts the difference in PTH values over time between two groups. No Significant changes were observed in the serum PTH levels at baseline (p-value=0.170). At 6th week, the mean value of the PTH decreased from the baseline in both the group I and group O. No significant difference was observed between the groups at 6th week (p-value=0.801) and 12th week (p-value=0.371).


In present study, 86.67 % were found to be vitamin D deficient and 13.33% were Vitamin D insufficient according to Holick MF (Global Prospective 2013) (2).

Zhang D et al., did the study on 527 patients, 71% of the patients with fracture had low vitamin D levels (22). In a study by Hershkovitz A et al., 92.6% of the patients had lower cholecalciferol levels, in which 78.2% were vitamin D deficient and 14.4% were vitamin D insufficient. 6.8% of the patients had optimal vitamin D level. Cholecalciferol deficiency was found in 20.3% of the patients (23).

The vitamin D mean value was significantly raised with the time in group I and group O at 6th weeks and still remained increased at 12th weeks in group I but not in group O which implied better results in vitamin D level in group I, as compared to group O. Billoo A et al., and Hashemipour S et al., have done similar studies comparing two different routes for Vitamin D supplementation and found similar results (24),(25).

Previous studies by Robertson DS et al.,; Gupta N et al., and Lakkireddy M et al., reported similar observations regarding the safety, efficacy and acceptability of a single dose of vitamin D versus oral vitamin D (20),(26),(27). Vitamin D (cholecalciferol) was found to be helpful in both oral and injectable forms. The vitamin D value at 6th weeks increased for both groups 40.94±4.67 ng/mL for group I and 33.64±9.89 ng/mL for group O as compared to their baseline values which were 13.84±3.54 ng/mL and 16.45±6.3 ng/mL for group I and group O respectively.

Although the results after administration of injectable form were statistically significant as at 12th weeks vitamin D values sustained and showed increase in injectable group compared to group O as evident from the values 44.52±7.09 ng/mL for group I and 24.65± 10.92 ng/mL for group O. There were no negative side effects, and both treatment options were well tolerated.

Significant changes were observed in the serum calcium levels from baseline within the groups which declined at 6th weeks followed by rise at 12th weeks. Statistically no significant difference was observed in the mean calcium levels between both the groups at 12th weeks. These observations were similar with studies conducted by Mittal H et al., (28). They investigated the non-inferiority of a lower therapeutic dose (3,00,000 IU) of vitamin D for boosting blood 25(OH) D levels when compared to a conventional dose (600,000 IU) (28). They discovered hypercalcemia in two children at 4th weeks (one in each group) and three children at 12th weeks (one in group 1 and two in group 2). It was concluded that initially calcium level were decreased initially and then increased.

Difference was observed in the serum ALP from baseline within the groups. The mean serum ALP which in both the groups decreased at 6th and 12th weeks. Statistically no significant difference was observed in the mean ALP levels between both the groups at 12th weeks. This was similar to the outcome of the study conducted by Mittal H et al, both the groups demonstrated significant (p-value<0.05) and comparable fall in the serum alkaline phosphatase levels at 12th weeks (28).

Vitamin D deficiency have been observed to often have raised serum PTH levels. The mean serum PTH respectively in the group I and group O which showed a significant decrease in the levels at 6th weeks and 12th weeks. Statistically no significant difference was observed in the mean PTH levels between both the groups at 12 weeks. The PTH values were higher than normal range in many patients and may be attributed to higher ages of the subjects. This finding is consistent with that reported by Haden ST et al., where it was observed that both the study groups demonstrated significant (p-value <0.05) and comparable fall in the serum parathormone levels at 12 weeks. Relative change {ratio of geometric mean (95% CI)} in serum PTH, 12th weeks after therapy, were 0.98 (0.7-1.47) (29). Choi HK et al., assessed the efficacy and safety of high-dose vitamin D3 after intramuscular injection and found that decreased levels of PTH in the vitamin D3 group when compared to control group (30). Haden ST et al., also observed that in both the groups, efficacious PTH suppression were observed. A single intramuscular dose of vitamin D3 had no meaningful effect on parathyroid hormone. It was concluded that both the groups showed statistically significant suppression of PTH from baseline (29).

Reduced vitamin D levels may also have a role in the occurrence of hip fractures in these older people, especially if they also have osteoporosis, as suggested by the data. These studies demonstrated that calcium and vitamin D supplementation is safe and induced a moderate reduction in femoral neck bone loss associated with a substantial reduction of the risk of hip fracture in elderly ambulatory women. Previous research by Sanfelix-Genovés J et al., and Diez A et al., has shown that oral vitamin D replacement has a low rate of compliance (31),(32). Pearce SH and Cheetham TD, suggested an i.m. dose of 300,000 IU cholecalciferol once a month for 3 months followed by the same dose once or twice a year in patients with severe malabsorption (33). The pharmacokinetics of i.m. D3 delivery, as well as the lack of 25(OH)D level variations after i.m. treatment, makes it a good therapeutic choice for people who have obesity, malabsorption, or compliance issues as suggested by Vieth R (34). Kaur P et al., found that excessive doses and injudicious usage of the parenteral route, on the other hand, may be linked to problems including hypercalcemia, hypercalciuria, and vitamin D toxicity (35).


Outcome of hip fractures could not be taken into consideration on oral versus intramuscular vitamin D injection.


Present study established an association between hypovitaminosis D and intramuscular injection of vitamin D. It was concluded that although both administration routes are effective and appear to be safe, intramuscular application is more effective in increasing 25(OH)D levels and sustaining it for a longer period of time as compared to oral dose. Identifying and treating these patients early with vitamin D for osteomalacia and anti osteoporotic regimens for osteoporosis will improve the bone, muscle and overall health thereby reducing falls and fractures. Studies on larger scale are needed to be carried out to set the inferences on right dosage of vitamin D.


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DOI and Others

DOI: 10.7860/JCDR/2022/56181.16475

Date of Submission: Mar 09, 2022
Date of Peer Review: Mar 22, 2022
Date of Acceptance: May 09, 2022
Date of Publishing: Jun 01, 2022

• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA

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